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1.
Adv Exp Med Biol ; 1232: 409-414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893438

RESUMO

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP669-711/Aß1-42 and Aß1-40/Aß1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Humanos
2.
Biosci Biotechnol Biochem ; 84(1): 1-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31538538

RESUMO

Recent investigations suggest that soluble oligomeric amyloid ß (Aß) species may be involved in early onset of Alzheimer's disease (AD). Using systematic proline replacement, solid-state NMR, and ESR, we identified a toxic turn at position 22 and 23 of Aß42, the most potent neurotoxic Aß species. Through radicalization, the toxic turn can induce formation of the C-terminal hydrophobic core to obtain putative Aß42 dimers and trimers. Synthesized dimer and trimer models showed that the C-terminal hydrophobic core plays a critical role in the formation of high molecular weight oligomers with neurotoxicity. Accordingly, an anti-toxic turn antibody (24B3) that selectively recognizes a toxic dimer model of E22P-Aß42 was developed. Sandwich enzyme-linked immunosorbent assay with 24B3 and 82E1 detected a significantly higher ratio of Aß42 with a toxic turn to total Aß42 in cerebrospinal fluid of AD patients compared with controls, suggesting that 24B3 could be useful for early onset of AD diagnosis.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/imunologia , Anticorpos Monoclonais/uso terapêutico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fragmentos de Peptídeos/imunologia , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/química , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Camundongos , Modelos Moleculares , Emaranhados Neurofibrilares/química , Fragmentos de Peptídeos/química , Placa Amiloide/química , Prolina/química , Agregados Proteicos , Agregação Patológica de Proteínas , Estrutura Terciária de Proteína
4.
Biochemistry (Mosc) ; 84(11): 1346-1358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760922

RESUMO

Neprilysin (NEP) is a zinc-dependent metalloproteinase that exists in organisms in both transmembrane and soluble forms. NEP substrates are involved in regulating the cardiovascular and nervous systems. In this review, we discuss some of the biochemical characteristics and physiological functions of this enzyme with special emphasis on the use of NEP as a therapeutic target. The history and various physiological aspects of applying NEP inhibitors for treating heart failure and attempts to increase NEP activity when treating Alzheimer's disease using gene and cell therapies are described. Another important issue discussed is the role of NEP as a potential marker for predicting the risk of cardiovascular disease complications. The diagnostic and prognostic performance of soluble NEP in various types of heart failure is analyzed and presented. We also discuss the methods and approaches for measuring NEP activity for prognosis and diagnosis, as well as a possible new role of natriuretic peptides (NEP substrates) in cardiovascular diagnostics.


Assuntos
Doença de Alzheimer/diagnóstico , Neprilisina/metabolismo , Doença de Alzheimer/tratamento farmacológico , Biomarcadores/análise , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Neprilisina/análise , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Sistema Renina-Angiotensina , Yin-Yang
5.
BMC Neurol ; 19(1): 269, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684893

RESUMO

BACKGROUND: To determine whether items of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) could discriminate among cognitively normal controls (NC), and those with mild cognitive impairment (MCI), mild Alzheimer's disease (AD), and moderate-severe (AD), as well as their sensitivity and specificity. METHODS: MCI (n = 456), mild AD (n = 502) and moderate-severe AD (n = 102) patients were recruited from the memory clinic, Huashan Hospital, Shanghai, China. NC (n = 329) were recruited from health checkup outpatients. Five MoCA-BC item scores were collected in interviews. RESULTS: The MoCA-BC orientation test had high sensitivity and specificity for discrimination among MCI, mild AD and moderate-severe AD. The delayed recall memory test had high sensitivity and specificity for MCI screening. The verbal fluency test was efficient for detecting MCI and differentiating AD severity. CONCLUSIONS: Various items of the MoCA-BC can identify MCI patients early and identify the severity of dementia.


Assuntos
Doença de Alzheimer , Testes de Estado Mental e Demência , Doença de Alzheimer/classificação , Doença de Alzheimer/diagnóstico , China , Disfunção Cognitiva/classificação , Disfunção Cognitiva/diagnóstico , Humanos , Sensibilidade e Especificidade , Traduções
6.
Adv Exp Med Biol ; 1192: 27-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31705489

RESUMO

Alzheimer's disease is a complex and heterogeneous, severe neurodegenerative disorder and the predominant form of dementia, characterized by cognitive disturbances, behavioral and psychotic symptoms, progressive cognitive decline, disorientation, behavioral changes, and death. Genetic background of Alzheimer's disease differs between early-onset familial Alzheimer's disease, other cases of early-onset Alzheimer's disease, and late-onset Alzheimer's disease. Rare cases of early-onset familial Alzheimer's diseases are caused by high-penetrant mutations in genes coding for amyloid precursor protein, presenilin 1, and presenilin 2. Late-onset Alzheimer's disease is multifactorial and associated with many different genetic risk loci (>20), with the apolipoprotein E ε4 allele being a major genetic risk factor for late-onset Alzheimer's disease. Genetic and genomic studies offer insight into many additional genetic risk loci involved in the genetically complex nature of late-onset Alzheimer's disease. This review highlights the contributions of individual loci to the pathogenesis of Alzheimer's disease and suggests that their exact contribution is still not clear. Therefore, the use of genetic markers of Alzheimer's disease, for monitoring development, time course, treatment response, and prognosis of Alzheimer's disease, is still far away from the clinical application, because the contribution of genetic variations to the relative risk of developing Alzheimer's disease is limited. In the light of prediction and prevention of Alzheimer's disease, a novel approach could be found in the form of additive genetic risk scores, which combine additive effects of numerous susceptibility loci.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Presenilina-1/genética , Presenilina-2/genética , Doença de Alzheimer/diagnóstico , Precursor de Proteína beta-Amiloide , Apolipoproteínas E , Marcadores Genéticos , Humanos
8.
JAMA ; 322(16): 1589-1599, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638686

RESUMO

Importance: Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million. Observations: Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia. Conclusions and Relevance: Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited.


Assuntos
Demência/diagnóstico , Demência/terapia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Memantina/efeitos adversos , Memantina/uso terapêutico , Neuroimagem , Testes Neuropsicológicos
9.
Einstein (Sao Paulo) ; 18: eAO4752, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31664323

RESUMO

OBJECTIVE: To evaluate the epidemiological profile of patients seen at a dementia outpatient clinic. METHODS: A retrospective study conducted by medical record review searching data on sex, race, age, schooling level, and diagnosis of patients seen from 2008 to 2015. RESULTS: A total of 760 patients were studied, with a predominance of female (61.3%; p<0.0001). The mean age was 71.2±14.43 years for women and 66.1±16.61 years for men. The most affected age group was 71 to 80 years, accounting for 29.4% of cases. In relation to race, 96.3% of patients were white. Dementia was diagnosed in 68.8% of patients, and Alzheimer's disease confirmed in 48.9%, vascular dementia in 11.3%, and mixed dementia in 7.8% of cases. The prevalence of dementia was 3% at 70 years and 25% at 85 years. Dementia appeared significantly earlier in males (mean age 68.5±15.63 years). As to sex distribution, it was more frequent in women (59.6%) than in men (40.4%; p<0.0001; OR=2.15). People with higher schooling level (more than 9 years) had a significantly younger age at onset of dementia as compared to those with lower schooling level (1 to 4 years; p=0.0007). CONCLUSION: Most patients seen in the period presented dementia, and Alzheimer was the most prevalent disease. Women were more affected, and men presented young onset of the disease. Individuals with higher schooling level were diagnosed earlier than those with lower level.


Assuntos
Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Pacientes Ambulatoriais/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Brasil/epidemiologia , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Escolaridade , Feminino , Hospitais Privados/estatística & dados numéricos , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Adulto Jovem
10.
Nat Neurosci ; 22(11): 1903-1912, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31591557

RESUMO

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.


Assuntos
Doença de Alzheimer/metabolismo , Atlas como Assunto , Perfilação da Expressão Gênica , Lobo Parietal/metabolismo , /biossíntese , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Humanos , MicroRNAs/metabolismo , RNA Mensageiro/biossíntese , Análise de Sequência de RNA , Índice de Gravidade de Doença
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(5): 711-719, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31631618

RESUMO

Alzheimer's disease (AD) is a typical neurodegenerative disease, which is clinically manifested as amnesia, loss of language ability and self-care ability, and so on. So far, the cause of the disease has still been unclear and the course of the disease is irreversible, and there has been no cure for the disease yet. Hence, early prognosis of AD is important for the development of new drugs and measures to slow the progression of the disease. Mild cognitive impairment (MCI) is a state between AD and healthy controls (HC). Studies have shown that patients with MCI are more likely to develop AD than those without MCI. Therefore, accurate screening of MCI patients has become one of the research hotspots of early prognosis of AD. With the rapid development of neuroimaging techniques and deep learning, more and more researchers employ deep learning methods to analyze brain neuroimaging images, such as magnetic resonance imaging (MRI), for early prognosis of AD. Hence, in this paper, a three-dimensional multi-slice classifiers ensemble based on convolutional neural network (CNN) and ensemble learning for early prognosis of AD has been proposed. Compared with the CNN classification model based on a single slice, the proposed classifiers ensemble based on multiple two-dimensional slices from three dimensions could use more effective information contained in MRI to improve classification accuracy and stability in a parallel computing mode.


Assuntos
Doença de Alzheimer/diagnóstico , Aprendizado Profundo , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva , Humanos , Neuroimagem , Prognóstico
12.
Cochrane Database Syst Rev ; 9: CD011414, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521064

RESUMO

BACKGROUND: The diagnosis of Alzheimer's disease dementia and other dementias relies on clinical assessment. There is a high prevalence of cognitive disorders, including undiagnosed dementia in secondary care settings. Short cognitive tests can be helpful in identifying those who require further specialist diagnostic assessment; however, there is a lack of consensus around the optimal tools to use in clinical practice. The Mini-Cog is a short cognitive test comprising three-item recall and a clock-drawing test that is used in secondary care settings. OBJECTIVES: The primary objective was to determine the diagnostic accuracy of the Mini-Cog for detecting Alzheimer's disease dementia and other dementias in a secondary care setting. The secondary objectives were to investigate the heterogeneity of test accuracy in the included studies and potential sources of heterogeneity. These potential sources of heterogeneity will include the baseline prevalence of dementia in study samples, thresholds used to determine positive test results, the type of dementia (Alzheimer's disease dementia or all causes of dementia), and aspects of study design related to study quality. SEARCH METHODS: We searched the following sources in September 2012, with an update to 12 March 2019: Cochrane Dementia Group Register of Diagnostic Test Accuracy Studies, MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We made no exclusions with regard to language of Mini-Cog administration or language of publication, using translation services where necessary. SELECTION CRITERIA: We included cross-sectional studies and excluded case-control designs, due to the risk of bias. We selected those studies that included the Mini-Cog as an index test to diagnose dementia where dementia diagnosis was confirmed with reference standard clinical assessment using standardised dementia diagnostic criteria. We only included studies in secondary care settings (including inpatient and outpatient hospital participants). DATA COLLECTION AND ANALYSIS: We screened all titles and abstracts generated by the electronic database searches. Two review authors independently checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies, reporting the sensitivity, specificity, and 95% confidence intervals of these measures, summarising them graphically using forest plots. MAIN RESULTS: Three studies with a total of 2560 participants fulfilled the inclusion criteria, set in neuropsychology outpatient referrals, outpatients attending a general medicine clinic, and referrals to a memory clinic. Only n = 1415 (55.3%) of participants were included in the analysis to inform evaluation of Mini-Cog test accuracy, due to the selective use of available data by study authors. There were concerns related to high risk of bias with respect to patient selection, and unclear risk of bias and high concerns related to index test conduct and applicability. In all studies, the Mini-Cog was retrospectively derived from historic data sets. No studies included acute general hospital inpatients. The prevalence of dementia ranged from 32.2% to 87.3%. The sensitivities of the Mini-Cog in the individual studies were reported as 0.67 (95% confidence interval (CI) 0.63 to 0.71), 0.60 (95% CI 0.48 to 0.72), and 0.87 (95% CI 0.83 to 0.90). The specificity of the Mini-Cog for each individual study was 0.87 (95% CI 0.81 to 0.92), 0.65 (95% CI 0.57 to 0.73), and 1.00 (95% CI 0.94 to 1.00). We did not perform meta-analysis due to concerns related to risk of bias and heterogeneity. AUTHORS' CONCLUSIONS: This review identified only a limited number of diagnostic test accuracy studies using Mini-Cog in secondary care settings. Those identified were at high risk of bias related to patient selection and high concerns related to index test conduct and applicability. The evidence was indirect, as all studies evaluated Mini-Cog differently from the review question, where it was anticipated that studies would conduct Mini-Cog and independently but contemporaneously perform a reference standard assessment to diagnose dementia. The pattern of test accuracy varied across the three studies. Future research should evaluate Mini-Cog as a test in itself, rather than derived from other neuropsychological assessments. There is also a need for evaluation of the feasibility of the Mini-Cog for the diagnosis of dementia to help adequately determine its role in the clinical pathway.


Assuntos
Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Testes de Estado Mental e Demência , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Progressão da Doença , Humanos , Testes de Estado Mental e Demência/normas , Atenção Secundária à Saúde , Sensibilidade e Especificidade
15.
Anal Chim Acta ; 1082: 106-115, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472699

RESUMO

Sphingoid bases (SBs) are one of important components of cell membranes, playing important roles in cellular biology. Meanwhile, SBs are associated with various metabolic diseases such as Type 2 Diabetes mellitus (T2DM). Therefore, simultaneous quantitation of multiple SBs in biological samples could provide crucial information for uncovering underlying mechanisms of SBs related functions and diseases. However, existing methods are difficult to achieve simultaneous quantitation for multiple SBs due to the lack of isotope internal standards (ISs) of corresponding SBs. In the current study, we developed a highly sensitive method for the simultaneous detection of 26 SBs in biological samples by stable isotope labeling coupled with ultra-high performance liquid chromatography tandem mass spectrometry (SIL-UHPLC-MS/MS) analysis. In this respect, a pair of isotope labeling reagents, 3-(N, N-dimethylamino)propyl isothiocyanate (DMPI) and d4-3-(N, N-dimethylamino)propyl isothiocyanate (d4-DMPI), were synthesized and utilized to label SBs in biological samples and SB standards, respectively. The d4-DMPI labeled SB standards were used as ISs to calibrate quantitation deviation in MS analysis from the biological matrix. Using the developed method, we successfully quantitated 19 SBs in cells, 20 SBs in mice feces and 18 SBs in human serum samples. Three C17-SBs used as ISs in many reported works were even found in all prepared samples. In summary, the developed SIL-UHPLC-MS/MS analysis was demonstrated to be a promising method for the simultaneous determination of multiple SBs, which could facilitate the investigation of cellular function of SBs and pathogenesis of related diseases.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Esfingolipídeos/sangue , Espectrometria de Massas em Tandem/métodos , Doença de Alzheimer/diagnóstico , Animais , Biomarcadores/sangue , Biomarcadores/química , Linhagem Celular Tumoral , Deutério , Diabetes Mellitus Tipo 2/diagnóstico , Fezes/química , Humanos , Isotiocianatos/química , Marcação por Isótopo/métodos , Limite de Detecção , Camundongos , Esfingolipídeos/química
17.
Dement Geriatr Cogn Disord ; 47(4-6): 281-288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31408867

RESUMO

BACKGROUND: Although simple reaction time (SRT) slowing is associated with dementia in Alzheimer's disease (AD), its presence in individuals with mild cognitive impairment (MCI) is subject to debate. OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis of the literature data on SRT slowing in MCI. METHODS: Publications with data on SRT, age, and educational level in participants with MCI were included. After calculating the log SRT and its variance for each study, we took interstudy heterogeneity into account by conducting a random effects (restricted maximum likelihood estimation) meta-analysis. RESULTS: The 7 selected studies featured a total of 327 participants with MCI and 468 healthy controls (HCs). The mean age was 68.2 years for participants with MCI and 72.3 years for HCs. The weighted mean Mini-Mental State Examination score was 26.4 in the MCI group, and 28.4 in the HC group. The mean SRT was significantly (p = 0.0217) longer in the MCI group (by 11%) than in the HC group. CONCLUSION: This meta-analysis showed that SRTs are longer in individuals with MCI. Further studies are needed to determine the mechanism of SRT slowing, its anatomical correlates, and a threshold value for diagnosing prodromal AD.


Assuntos
Doença de Alzheimer/psicologia , Tempo de Reação , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/psicologia , Diagnóstico Precoce , Humanos , Pessoa de Meia-Idade
18.
Int J Nanomedicine ; 14: 5541-5554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410002

RESUMO

Currently, 47 million people live with dementia globally, and it is estimated to increase more than threefold (~131 million) by 2050. Alzheimer's disease (AD) is one of the major causative factors to induce progressive dementia. AD is a neurodegenerative disease, and its pathogenesis has been attributed to extracellular aggregates of amyloid ß (Aß) plaques and intracellular neurofibrillary tangles made of hyperphosphorylated τ-protein in cortical and limbic areas of the human brain. It is characterized by memory loss and progressive neurocognitive dysfunction. The anomalous processing of APP by ß-secretases and γ-secretases leads to production of Aß40 and Aß42 monomers, which further oligomerize and aggregate into senile plaques. The disease also intensifies through infectious agents like HIV. Additionally, during disease pathogenesis, the presence of high concentrations of Aß peptides in central nervous system initiates microglial infiltration. Upon coming into vicinity of Aß, microglia get activated, endocytose Aß, and contribute toward their clearance via TREM2 surface receptors, simultaneously triggering innate immunoresponse against the aggregation. In addition to a detailed report on causative factors leading to AD, the present review also discusses the current state of the art in AD therapeutics and diagnostics, including labeling and imaging techniques employed as contrast agents for better visualization and sensing of the plaques. The review also points to an urgent need for nanotechnology as an efficient therapeutic strategy to increase the bioavailability of drugs in the central nervous system.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Barreira Hematoencefálica/patologia , Epigênese Genética , Humanos , Nanotecnologia , Placa Amiloide/patologia
19.
Nervenarzt ; 90(9): 907-913, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31407045

RESUMO

In accordance with the current German dementia guidelines, the dementia biomarkers amyloid beta 42, the tau peptides total tau and phosphorylated tau 181 are recommended for cerebrospinal fluid (CSF)-based diagnostics of dementia. Several studies have clearly shown that determination of the amyloid beta 42 to amyloid beta 40 peptide ratio is superior to the interpretation of amyloid beta 42 alone and should be implemented in the clinical work-up; however, in recent years different studies have presented many other innovative CSF and blood-based biomarkers. Besides CSF-based neurochemical diagnostics of dementia promising novel protocols for the detection of amyloid beta peptides in blood have meanwhile been published, which can currently be used in clinical studies for blood-based early diagnostics of Alzheimer's dementia. Following further validation and assay optimization these blood assays should be available for routine diagnostics in the near future.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Humanos
20.
Chem Commun (Camb) ; 55(70): 10424-10427, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31407744

RESUMO

The development of sensitive and reliable fluorescent probes for the early diagnosis of Alzheimer's disease (AD) is highly challenging and plays an important role in achieving effective treatments. Herein, we designed and synthesized an indole-based fluorophore for TTR in human plasma, an important hallmark of AD pathogenesis. This robust and simple fluorescent method allows quantification of TTR in the complex biological matrix.


Assuntos
Doença de Alzheimer/diagnóstico , Corantes Fluorescentes/química , Pré-Albumina/metabolismo , Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/metabolismo , Humanos , Limite de Detecção , Espectrometria de Fluorescência
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