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1.
Int J Mol Sci ; 25(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38892250

RESUMEN

Neurodegenerative diseases are progressive disorders that affect the central nervous system (CNS) and represent the major cause of premature death in the elderly. One of the possible determinants of neurodegeneration is the change in mitochondrial function and content. Altered levels of mitochondrial DNA copy number (mtDNA-CN) in biological fluids have been reported during both the early stages and progression of the diseases. In patients affected by neurodegenerative diseases, changes in mtDNA-CN levels appear to correlate with mitochondrial dysfunction, cognitive decline, disease progression, and ultimately therapeutic interventions. In this review, we report the main results published up to April 2024, regarding the evaluation of mtDNA-CN levels in blood samples from patients affected by Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The aim is to show a probable link between mtDNA-CN changes and neurodegenerative disorders. Understanding the causes underlying this association could provide useful information on the molecular mechanisms involved in neurodegeneration and offer the development of new diagnostic approaches and therapeutic interventions.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Mitocondrias , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/genética , ADN Mitocondrial/genética , Mitocondrias/genética , Mitocondrias/metabolismo , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Animales
2.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000146

RESUMEN

Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP, PSEN1, PSEN2, MAPT, GRN, and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1, 11 MAPT, 9 PSEN2, and 4 APP. Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.


Asunto(s)
Enfermedad de Alzheimer , Demencia Frontotemporal , Mutación , Proteínas tau , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Italia/epidemiología , Demencia Frontotemporal/genética , Demencia Frontotemporal/epidemiología , Demencia Frontotemporal/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Proteínas tau/genética , Edad de Inicio , Proteína C9orf72/genética , Presenilina-2/genética , Estudios Retrospectivos , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Progranulinas/genética , Adulto , Anciano de 80 o más Años , Predisposición Genética a la Enfermedad
3.
Immun Ageing ; 20(1): 16, 2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37038200

RESUMEN

BACKGROUND: Immunosenescence is a complex process characterized by an age-related remodelling of immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages. METHODS AND FINDINGS: By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents from Calabria (Southern Italy) was evaluated to investigate the relationship between thymic function and survival at old ages. We found that low sjTREC levels were associated with a significant increased risk of mortality at older ages. Nursing home residents with lower sjTREC exhibit a near 2-fold increase in mortality risk compared to those with sjTREC levels in a normal range. CONCLUSION: Thymic function failure is an independent predictor of mortality among elderly nursing home residents. sjTREC represents a biomarker of effective ageing as its blood levels could anticipate individuals at high risk of negative health outcomes. The identification of these subjects is crucial to manage older people's immune function and resilience, such as, for instance, to plan more efficient vaccinal campaigns in older populations.

4.
Int J Mol Sci ; 24(4)2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36834612

RESUMEN

Alzheimer's disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aß) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aß peptides can blind to NGFR/p75NTR making it the "ideal" candidate in mediating Aß-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.


Asunto(s)
Enfermedad de Alzheimer , Anciano , Animales , Humanos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Mamíferos/metabolismo , Factor de Crecimiento Nervioso/farmacología , Proteínas del Tejido Nervioso , Receptor de Factor de Crecimiento Nervioso/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , Proteínas tau/metabolismo
5.
Mov Disord ; 34(12): 1919-1924, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31755148

RESUMEN

BACKGROUND: Dentatorubral-pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral-pallidoluysian atrophy familial cases describing their clinical features. METHODS: We investigated 6 apparently unrelated dentatorubral-pallidoluysian atrophy families comprising a total of 51 affected individuals: 13 patients were clinically examined, and for 38 patients clinical data were collected from clinical sources. The dentatorubral-pallidoluysian atrophy diagnosis was genetically confirmed in 18 patients. Genealogical data from historical archives were analyzed. RESULTS: All 6 families were unified in a large pedigree deriving from a founder couple originating from Monte San Giuliano (Italy) in the late 1500s, with 51 affected subjects over the last 4 generations. Wide phenotypical variability in age at onset and clinical features was confirmed. Epilepsy was more frequent in juvenile cases than in late adults, with cognitive/psychiatric and motor disorders observed regardless of age at onset. CONCLUSIONS: We have described the largest Caucasian dentatorubral-pallidoluysian atrophy pedigree from a single founder couple. The introduction of the dentatorubral-pallidoluysian atrophy gene in Italy could have arisen as a result of trade relationships between the Spanish or Portuguese and the Japanese in the 1500s. © 2019 International Parkinson and Movement Disorder Society.


Asunto(s)
Efecto Fundador , Mutación/genética , Epilepsias Mioclónicas Progresivas/epidemiología , Epilepsias Mioclónicas Progresivas/genética , Adolescente , Adulto , Anciano , Niño , Epilepsia/complicaciones , Epilepsia/epidemiología , Familia , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Epilepsias Mioclónicas Progresivas/psicología , Pruebas Neuropsicológicas , Linaje , Repeticiones de Trinucleótidos , Población Blanca , Adulto Joven
6.
Biochim Biophys Acta ; 1862(9): 1766-73, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27345265

RESUMEN

Maintenance of electric potential and synaptic transmission are energetically demanding tasks that neuronal metabolism must continually satisfy. Inability to fulfil these energy requirements leads to the development of neurodegenerative disorders, including Alzheimer's disease. A prominent feature of Alzheimer's disease is in fact neuronal glucose hypometabolism. Thus understanding the fine control of energetic metabolism might help to understand neurodegenerative disorders. Recent research has indicated that a novel class of signalling molecules, the inositol pyrophosphates, act as energy sensors. They are able to alter the balance between mitochondrial oxidative phosphorylation and glycolytic flux, ultimately affecting the cellular level of ATP. The neuronal inositol pyrophosphate synthesis relies on the activity of the neuron enriched inositol hexakisphosphate kinase 3 (IP6K3) enzyme. To verify an involvement of inositol pyrophosphate signalling in neurodegenerative disorders, we performed tagging single nucleotide polymorphism (SNP) analysis of the IP6K3 gene in patients with familial and sporadic late onset Alzheimer's disease (LOAD). Two SNPs in the 5'-flanking promoter region of the IP6K3 gene were found to be associated with sporadic LOAD. Characterizing the functionality of the two polymorphisms by luciferase assay revealed that one of them (rs28607030) affects IP6K3 promoter activity, with the G allele showing an increased activity. As the same allele has a beneficial effect on disease risk, this may be related to upregulation of IP6K3 expression, with a consequent increase in inositol pyrophosphate synthesis. In conclusion, we provide the first evidence for a contribution of genetic variability in the IP6K3 gene to LOAD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Región de Flanqueo 5' , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etiología , Estudios de Casos y Controles , Línea Celular , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Técnicas In Vitro , Desequilibrio de Ligamiento , Masculino , Fosfotransferasas (Aceptor del Grupo Fosfato)/metabolismo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas
7.
Hum Mol Genet ; 23(21): 5630-7, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24908669

RESUMEN

The G4C2-repeat expansion in C9orf72 is a common cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 transcription is reduced in expansion carriers implicating haploinsufficiency as one of the disease mechanisms. Indeed, our recent ALS study revealed that the expansion was associated with hypermethylation of the CpG-island (5'of the repeat) in DNA samples obtained from different tissues (blood, brain and spinal cord). However, the link between FTLD and methylation of the CpG-island is unknown. Hence, we investigated the methylation profile of the same CpG-island by bisulfite sequencing of DNA obtained from blood of 34 FTLD expansion carriers, 166 FTLD non-carriers and 103 controls. Methylation level was significantly higher in FTLD expansion carriers than non-carriers (P = 7.8E-13). Our results were confirmed by two methods (HhaI-assay and sequencing of cloned bisulfite PCR products). Hypermethylation occurred only in carriers of an allele with >50 repeats, and was not detected in non-carriers or individuals with an intermediate allele (22-43 repeats). As expected, the position/number of methylated CpGs was concordant between the sense and anti-sense DNA strand, suggesting that it is a stable epigenetic modification. Analysis of the combined ALS and FTLD datasets (82 expansion carriers) revealed that the degree of methylation of the entire CpG-island or contribution of specific CpGs (n = 26) is similar in both syndromes, with a trend towards a higher proportion of ALS patients with a high methylation level (P = 0.09). In conclusion, we demonstrated that hypermethylation of the CpG-island 5'of the G4C2-repeat is expansion-specific, but not syndrome-specific (ALS versus FTLD).


Asunto(s)
Islas de CpG , Metilación de ADN , Expansión de las Repeticiones de ADN , Degeneración Lobar Frontotemporal/genética , Proteínas/genética , Edad de Inicio , Anciano , Esclerosis Amiotrófica Lateral/genética , Proteína C9orf72 , Conjuntos de Datos como Asunto , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ADN
8.
Acta Neuropathol ; 129(5): 715-27, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25716178

RESUMEN

The most common cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a G4C2-repeat expansion in C9orf72. However, the lower limit for pathological repeats has not been established and expansions with different sizes could have different pathological consequences. One of the implicated disease mechanisms is haploinsufficiency. Previously, we identified expansion-specific hypermethylation at the 5' CpG-island near the G4C2-repeat, but only in a fraction of carriers (up to 36 %). Here, we tested the hypothesis that the G4C2-repeat itself could be the main site of methylation. To evaluate (G4C2)n -methylation, we developed a novel assay, which was validated by an independent methylation-sensitive restriction enzyme assay. Notably, both assays are qualitative but not quantitative. Blood DNA was available for 270 unrelated individuals, including 71 expansion carriers. In addition, we investigated blood DNA from family members of 16 probands, and 38 DNA samples from multiple tissues of 10 expansion carriers. Finally, we tested DNA from different tissues of an ALS patient carrying a somatically unstable 90-repeat. We demonstrated that the G4C2-expansion is generally methylated in unrelated carriers of alleles >50 repeats (97 %), while small (<22 repeats) or intermediate (22-90 repeats) alleles were completely unmethylated. The presence of (G4C2)n -methylation does not separate the C9orf72-phenotypes (ALS vs. ALS/FTLD vs. FTLD), but has the potential to predict large vs. intermediate repeat length. Our results suggest that (G4C2)n -methylation might sometimes spread to the 5'-upstream region, but not vice versa. It is stable over time, since (G4C2)n -methylation was detected in carriers with a wide range of ages (24-74 years). It was identified in both blood and brain tissues for the same individual, implying its potential use as a biomarker. Furthermore, our findings may open up new perspectives for studying disease mechanisms, such as determining whether methylated and unmethylated repeats have the same ability to form a G-quadruplex configuration.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Islas de CpG , Metilación de ADN , Expansión de las Repeticiones de ADN , Degeneración Lobar Frontotemporal/genética , Proteínas/genética , Anciano , Alelos , Proteína C9orf72 , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mapeo Restrictivo/métodos , Análisis de Secuencia de ADN
9.
Heliyon ; 10(11): e31624, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38828303

RESUMEN

The Forkhead box P2 (FOXP2) is an evolutionary conserved transcription factor involved in the maintenance of neuronal networks, implicated in language disorders. Some evidence suggests a possible link between FOXP2 genetic variability and frontotemporal dementia (FTD) pathology and related endophenotypes. To shed light on this issue, we analysed the association between single-nucleotide polymorphisms (SNPs) in FOXP2 and FTD in 113 patients and 223 healthy controls. In addition, we investigated SNPs in two putative targets of FOXP2, CNTNAP2, Contactin-associated protein-like 2 and PRNP, prion protein genes. Overall, 27 SNPs were selected by a tagging approach. FOXP2-rs17213159-C/T resulted associated with disease risk (OR = 2.16, P = 0.0004), as well as with age at onset and severity of dementia. Other FOXP2 markers were associated with semantic and phonological fluency scores, cognitive levels (MMSE) and neuropsychological tests. Associations with language, cognitive and brain atrophy measures were found with CNTNAP2 and PRNP genetic variability. Overall, although preliminary, results here presented suggest an influence of regulatory pathways centred on FOXP2 as a molecular background of FTD affecting neurological function of multiple brain areas.

10.
Biology (Basel) ; 12(10)2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37886996

RESUMEN

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are markers of premature cellular senescence. This may contribute to age-related diseases, including Alzheimer's disease (AD), and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, who were all from Calabria, a southern Italian region. Following regression analysis, telomeres were found significantly shorter in LOAD cases than in controls (48% and 41% decrease for sporadic and familial cases, respectively; p < 0.001 for both). Interestingly, LTL was associated with disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, and the presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the pathogenesis of LOAD.

11.
Ageing Res Rev ; 91: 102068, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37704050

RESUMEN

Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. Two major forms of the disease exist: sporadic - the causes of which have not yet been fully understood - and familial - inherited within families from generation to generation, with a clear autosomal dominant transmission of mutations in Presenilin 1 (PSEN1), 2 (PSEN2) or Amyloid Precursors Protein (APP) genes. The main hallmark of AD consists of extracellular deposits of amyloid-beta (Aß) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein. An ever-growing body of research supports the viral infectious hypothesis of sporadic forms of AD. In particular, it has been shown that several herpes viruses (i.e., HHV-1, HHV-2, HHV-3 or varicella zoster virus, HHV-4 or Epstein Barr virus, HHV-5 or cytomegalovirus, HHV-6A and B, HHV-7), flaviviruses (i.e., Zika virus, Dengue fever virus, Japanese encephalitis virus) as well as Human Immunodeficiency Virus (HIV), hepatitis viruses (HAV, HBV, HCV, HDV, HEV), SARS-CoV2, Ljungan virus (LV), Influenza A virus and Borna disease virus, could increase the risk of AD. Here, we summarized and discussed these results. Based on these findings, significant issues for future studies are also put forward.


Asunto(s)
Enfermedad de Alzheimer , Infecciones por Virus de Epstein-Barr , Virosis , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , ARN Viral , Herpesvirus Humano 4/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Virosis/complicaciones , Virus Zika/genética , Virus Zika/metabolismo
12.
Curr Oncol ; 29(11): 8103-8120, 2022 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-36354700

RESUMEN

Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017.


Asunto(s)
Neoplasias de la Mama , Factor de Crecimiento Nervioso , Femenino , Humanos , Factor de Crecimiento Nervioso/metabolismo , Factor de Crecimiento Nervioso/farmacología , Receptor trkA/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Receptor de Factor de Crecimiento Nervioso , Transducción de Señal/fisiología
13.
Biomedicines ; 10(9)2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36140389

RESUMEN

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology-ranging from clinical activity to the genealogical reconstruction of families/populations across the centuries, the creation of databases, and molecular/genetic research-was modelled on the characteristics of the Calabrian population for more than three decades. This methodology allowed the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, a higher prevalence of several hereditary neurodegenerative diseases has been reported in this population, such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Niemann-Pick type C disease, spinocerebellar ataxia, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker disease. Here, we summarize and discuss the results of research data supporting the view that Calabria could be considered as a genetic isolate and could represent a model, a sort of outdoor laboratory-similar to very few places in the world-useful for the advancement of knowledge on neurodegenerative diseases.

14.
J Alzheimers Dis ; 85(2): 691-699, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34864668

RESUMEN

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) have a large impact on the quality of life of patients with Alzheimer's disease (AD). Few studies have compared BPSD between early-onset (EOAD) and late-onset (LOAD) patients, finding conflicting results. OBJECTIVE: The aims of this study were to: 1) characterize the presence, overall prevalence, and time of occurrence of BPSD in EOAD versus LOAD; 2) estimate the prevalence over time and severity of each BPSD in EOAD versus LOAD in three stages: pre-T0 (before the onset of the disease), T0 (from onset to 5 years), and T1 (from 5 years onwards); 3) track the manifestation of BPSD sub-syndromes (i.e., hyperactivity, psychosis, affective, and apathy) in EOAD versus LOAD at T0 and T1. METHODS: The sample includes 1,538 LOAD and 387 EOAD diagnosed from 1996 to 2018. Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment and at different follow-up period. RESULTS: The overall prevalence for the most of BPSD was significantly higher in EOAD compared to LOAD whereas most BPSD appeared significantly later in EOAD patients. Between the two groups, from pre-T0 to T1 we recorded a different pattern of BPSD prevalence over time as well as for BPSD sub-syndromes at T0 and T1. Results on severity of BPSD did not show significant differences. CONCLUSION: EOAD and LOAD represent two different forms of a single entity not only from a neuropathological, cognitive, and functional level but also from a psychiatric point of view.


Asunto(s)
Enfermedad de Alzheimer/psicología , Síntomas Conductuales/psicología , Pruebas Neuropsicológicas/estadística & datos numéricos , Síntomas Afectivos/psicología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Apatía , Demencia/complicaciones , Demencia/diagnóstico , Demencia/psicología , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Agitación Psicomotora/psicología , Trastornos Psicóticos/psicología , Índice de Severidad de la Enfermedad
15.
Front Psychol ; 13: 923316, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35911007

RESUMEN

People with dementia have an increased risk of contracting severe forms of COVID-19. Although in worldwide vaccination programs priority has been given to older people, having taken the vaccine does not totally eliminate the risk of contracting COVID-19 when one is in close contact with unvaccinated people. Thus, family caregivers' choices to remain unvaccinated against COVID-19 could have potentially lethal consequences for their relatives. To our knowledge, this study represents the first attempt within the international literature to analyze COVID-19 vaccine uptake among family caregivers of people with dementia and to identify some of the psychological factors, related to COVID-19 and vaccination behavior, that could facilitate or hinder vaccine uptake. Contact information for family caregivers was obtained from five different centers and associations throughout the Italian territory. Data were collected from 179 respondents during July-September 2021 using a cross-sectional web-based survey design. More than 75% of the respondents indicated that had been vaccinated against COVID-19 and reported receiving vaccine information mainly from print or electronic newspapers (86%), followed by TV (81%) and families (64.2%). In multivariable logistic regression analyses, worries about unforeseen future effects was significantly related to COVID-19 vaccine uptake, indicating that family caregivers concerned about potential side effects of vaccines were less likely to have been vaccinated against COVID-19 (OR = 0.60, CI = 0.40-0.89). Openness to experience was also related to COVID-19 vaccine uptake, with family caregivers higher on this trait being less likely to have been vaccinated against COVID-19 (OR = 0.83, CI = 0.71-0.98). Implications for targeting of vaccine-related messages are discussed.

16.
Front Neurol ; 13: 832199, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812082

RESUMEN

Neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD) represent a heterogeneous group of non-cognitive symptoms that are virtually present in all patients during the course of their disease. The aim of this study is to examine the prevalence and natural history of BPSD in a large cohort of patients with behavioral variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) in three stages: (i) pre-T0 (before the onset of the disease); (ii) T0 or manifested disease (from the onset to 5 years); (iii) T1 or advanced (from 5 years onwards). Six hundred seventy-four clinical records of patients with bvFTD and 1925 with AD, from 2006 to 2018, were studied. Symptoms have been extracted from Neuropsychiatric Inventory (NPI) and from a checklist of BPSD for all periods observed. In our population, BPSD affect up to 90% of all dementia subjects over the course of their illness. BPSD profiles of the two dementia groups were similar but not identical. The most represented symptoms were apathy, irritability/affective lability, and agitation/aggression. Considering the order of appearance of neuropsychiatric symptoms in AD and bvFTD, mood disorders (depression, anxiety) come first than the other BPSD, with the same prevalence. This means that they could be an important "red flag" in detection of dementia. With the increase of disease severity, aberrant motor behavior and wandering were significantly more present in both groups. Differences between BPSD in AD and bvFTD resulted only in prevalence: Systematically, in bvFTD, all the symptoms were more represented than in AD, except for hallucinations, depression, anxiety, and irritability. Given their high frequency and impact on management and overall health care resources, BPSD should not be underestimated and considered as an additional important diagnostic and therapeutic target both in patients with AD and bvFTD.

17.
Alzheimer Dis Assoc Disord ; 25(1): 96-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21343707

RESUMEN

The V363I mutation of the microtubule-associated protein tau gene has previously been associated with a case of primary progressive nonfluent aphasia with variable penetrance. Herein, we report the finding of the V363I variation in a sporadic early onset frontotemporal dementia patient and in several members of her family. The V363I variation was associated with frontotemporal dementia only in the proband which was also homozygous for the A allele of the progranulin single-nucleotide polymorphism rs9897526 and for methionine at codon 129 of the prion protein gene. The microtubule-associated protein tau V363I variation could be considered either an incomplete penetrant mutation or a rare polymorphism; although its pathogenicity has yet to be clearly demonstrated, modifier genetic factors seem to contribute to the pathogenic effects observed in the patient underlining the great complexity existing in neurodegenerative diseases and questioning so-called sporadic cases that can potentially be caused by gene mutation.


Asunto(s)
Demencia Frontotemporal/genética , Mutación , Polimorfismo de Nucleótido Simple , Proteínas tau/genética , Femenino , Demencia Frontotemporal/patología , Humanos , Masculino , Persona de Mediana Edad , Linaje
19.
Curr Opin Pharmacol ; 60: 275-280, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34487952

RESUMEN

Genetic testing for Alzheimer's disease offers a molecular diagnosis to patients and their relatives and provides information on personal risk, reproductive choices, clinical trial eligibility, and treatment options. In the past, molecular testing was limited to detecting single variations in single genes. Currently, with the advent of next-generation sequencing, simultaneous analysis of more than 100 genes using the same DNA sample is possible. This approach allows the determination of gene mutations, genetic risk factors, genotypes at many pharmacogenomic loci, and the determination of a polygenic risk scores for stratification of risk. This article reviews the diagnostic genetic testing of Alzheimer's disease, from the first molecular approaches to recent advances in NGS, focusing on a precision medicine approach.


Asunto(s)
Enfermedad de Alzheimer , Medicina de Precisión , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Farmacogenética
20.
Mech Ageing Dev ; 195: 111439, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33497757

RESUMEN

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein-protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits.


Asunto(s)
Envejecimiento/fisiología , Enfermedad de Alzheimer , Longevidad/fisiología , Mitocondrias/fisiología , Fosfotransferasas (Aceptor de Grupo Alcohol) , Fosfotransferasas (Aceptor del Grupo Fosfato) , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia/epidemiología , Masculino , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/metabolismo , Polimorfismo de Nucleótido Simple , Mapeo de Interacción de Proteínas/métodos , Transducción de Señal/fisiología
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