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1.
J Neurol Neurosurg Psychiatry ; 92(12): 1305-1312, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34187866

RESUMEN

BACKGROUND: Frontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD. METHODS: The levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients. RESULTS: sGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected. CONCLUSIONS: sGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.


Asunto(s)
Encéfalo/diagnóstico por imagen , Demencia Frontotemporal/diagnóstico , Proteína Ácida Fibrilar de la Glía/sangre , Anciano , Atrofia/sangre , Atrofia/diagnóstico por imagen , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Demencia Frontotemporal/sangre , Demencia Frontotemporal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Sensibilidad y Especificidad , Tasa de Supervivencia
2.
Dement Geriatr Cogn Disord ; 47(1-2): 91-103, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30861516

RESUMEN

BACKGROUND/AIMS: The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH). METHODS: We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age > 65 years). RESULTS: While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52-67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers. CONCLUSION: This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.


Asunto(s)
Esclerosis Amiotrófica Lateral , Síntomas Conductuales , Proteína C9orf72/genética , Degeneración Lobar Frontotemporal , Hidrocéfalo Normotenso , Edad de Inicio , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , Síntomas Conductuales/diagnóstico , Síntomas Conductuales/fisiopatología , Estudios de Cohortes , Correlación de Datos , Expansión de las Repeticiones de ADN , Femenino , Finlandia/epidemiología , Degeneración Lobar Frontotemporal/diagnóstico , Degeneración Lobar Frontotemporal/epidemiología , Degeneración Lobar Frontotemporal/genética , Humanos , Hidrocéfalo Normotenso/diagnóstico , Hidrocéfalo Normotenso/genética , Hidrocéfalo Normotenso/psicología , Masculino , Prevalencia
3.
Neurology ; 103(5): e209694, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39141892

RESUMEN

BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). METHODS: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. RESULTS: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). DISCUSSION: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hidrocéfalo Normotenso , Humanos , Hidrocéfalo Normotenso/genética , Femenino , Anciano , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Predisposición Genética a la Enfermedad/genética , Finlandia , Estudios de Cohortes , Polimorfismo de Nucleótido Simple , Anciano de 80 o más Años
4.
J Alzheimers Dis ; 93(2): 395-401, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37038815

RESUMEN

Frontotemporal dementia (FTD) can manifest as diverse clinical phenotypes and is frequently caused by mutations in different genes, complicating differential diagnosis. This underlines the urgent need for valid biomarkers. Altered lysosomal and immune functions proposedly contribute to FTD pathogenesis. Cathepsins, including cathepsin S, are enzymes preferentially expressed in brain in microglia, which influence lysosomal and immune function. Here, we examined whether alterations in serum cathepsin S levels associate with specific clinical, genetic, or neuropathological FTD subgroups, but no such alterations were observed. However, further research on other lysosomal proteins may reveal new biologically relevant biomarkers in FTD.


Asunto(s)
Demencia Frontotemporal , Humanos , Demencia Frontotemporal/diagnóstico , Proteínas tau/metabolismo , Encéfalo/patología , Mutación/genética , Biomarcadores , Catepsinas/genética , Catepsinas/metabolismo , Proteína C9orf72/genética
5.
Alzheimers Res Ther ; 14(1): 151, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36217158

RESUMEN

BACKGROUND: Frontotemporal dementia (FTD) covers a spectrum of neurodegenerative disorders with various clinical and neuropathological subtypes. The two major pathological proteins accumulating in the brains of FTD patients, depending on their genetic background, are TDP-43 and tau. We aimed to evaluate whether total TDP-43 levels measured from the serum associate with the genotype or clinical phenotype of the FTD patients and whether serum TDP-43 provides prognostic or diagnostic value in the FTD spectrum disorders. METHODS: The study cohort included 254 participants with a clinical diagnosis of FTD (including all major genotypes and clinical phenotypes) and 105 cognitively healthy controls. Serum total TDP-43 levels measured with a single-molecule array (Simoa) were compared within the FTD group according to the genotype, clinical phenotype, and predicted neuropathological subtype of the patients. We also evaluated the associations between the TDP-43 levels and disease severity or survival in FTD. RESULTS: Total TDP-43 levels in the serum were significantly lower in the FTD group as compared to the healthy control group (275.3 pg/mL vs. 361.8 pg/mL, B = 0.181, 95%CI = 0.014-0.348, p = 0.034). The lowest TDP-43 levels were observed in the subgroup of FTD patients harboring predicted TDP-43 brain pathology (FTD-TDP, 241.4 pg/mL). The low levels in the FTD-TDP group were especially driven by C9orf72 repeat expansion carriers (169.2 pg/mL) and FTD patients with concomitant motoneuron disease (FTD-MND, 113.3 pg/mL), whereas GRN mutation carriers did not show decreased TDP-43 levels (328.6 pg/mL). Serum TDP-43 levels showed no correlation with disease severity nor progression in FTD. CONCLUSIONS: Our results indicate that the total levels of TDP-43 in the serum are decreased especially in FTD patients with the C9orf72 repeat expansion or FTD-MND phenotype, both subtypes strongly associated with TDP-43 type B brain pathology. Serum-based measurement of TDP-43 could represent a useful tool in indicating C9orf72 repeat expansion and FTD-MND-related TDP-43 neuropathology for future diagnostics and intervention studies.


Asunto(s)
Proteína C9orf72 , Demencia Frontotemporal , Enfermedad de la Neurona Motora , Proteína C9orf72/genética , Expansión de las Repeticiones de ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Demencia Frontotemporal/patología , Humanos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/metabolismo , Enfermedad de la Neurona Motora/patología , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Fenotipo
6.
J Alzheimers Dis ; 80(4): 1629-1642, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33720890

RESUMEN

BACKGROUND: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. OBJECTIVE: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-ß (Aß) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. METHODS: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed Aß plaques in frontal cortical brain biopsy and 13 iNPH patients without Aß pathology. CSF Amyloid-ß42 (Aß42), total tau (T-tau), phosphorylated tau (P-tau181), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. RESULTS: All biomarkers but Aß42 increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. Aß42 instead showed divergent longitudinal decrease between Aß-positive and -negative patients in L-CSF, and thereafter increase in Aß-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (Aß42 R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (Aß42 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only Aß42 showed higher concentration in non-carriers of allele ɛ4. CONCLUSION: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy Aß pathology, while NFL normalized toward its pre-shunt levels. Aß42 as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V- than L-CSF yet showing strong correlations.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Hidrocéfalo Normotenso/líquido cefalorraquídeo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Derivaciones del Líquido Cefalorraquídeo , Femenino , Humanos , Hidrocéfalo Normotenso/patología , Hidrocéfalo Normotenso/cirugía , Masculino , Persona de Mediana Edad , Fosforilación , Análisis de Regresión , Medición de Riesgo
7.
J Neurol ; 267(1): 162-167, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31595378

RESUMEN

Due to the significant clinical overlap between frontotemporal lobar degeneration (FTLD) spectrum disorders and late-onset primary psychiatric disorders (PPD), diagnostic biomarkers reflecting the different underlying pathophysiologies are urgently needed. Thus far, elevated cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) have been reported in various neurological conditions. Furthermore, recent advancements in ultrasensitive analytical methods (e.g., single molecule array, Simoa) have enabled sensitive and less invasive NfL detection also from blood samples. In this study, we evaluated the potential of serum NfL (sNfL) as a diagnostic tool between FTLD and PPD. We analyzed sNfL levels with Simoa from 125 participants including patients from FTLD (n = 91) and PPD (n = 34) spectra. Our results show that sNfL levels are higher in the FTLD group compared to the PPD group as well as in separate clinical subtypes of FTLD compared to different psychiatric manifestations (i.e., mood or psychotic disorders). At single-subject level, discrimination between FTLD and PPD was possible with 80% sensitivity and 85% specificity (AUC = 0.850, 95% CI 0.776-0.923), and between behavioral variant frontotemporal dementia (bvFTD) and PPD with 79% sensitivity and 85% specificity (AUC = 0.830, 95% CI 0.732-0.908). These findings highlight the potential of sNfL as a discriminating biomarker for FTLD over PPD in patients with wide-ranging behavioral, psychiatric and cognitive symptoms.


Asunto(s)
Trastornos Psicóticos Afectivos/diagnóstico , Trastorno Bipolar/diagnóstico , Trastorno Depresivo/diagnóstico , Degeneración Lobar Frontotemporal/diagnóstico , Proteínas de Neurofilamentos/sangre , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Trastornos Psicóticos Afectivos/sangre , Anciano , Biomarcadores/sangre , Trastorno Bipolar/sangre , Trastorno Depresivo/sangre , Diagnóstico Diferencial , Femenino , Degeneración Lobar Frontotemporal/sangre , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/sangre , Esquizofrenia/sangre , Sensibilidad y Especificidad
8.
J Neurol ; 267(1): 76-86, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31559531

RESUMEN

In this study, our aim was to evaluate potential peripheral inflammatory changes in frontotemporal lobar degeneration (FTLD) patients carrying or not the C9orf72 repeat expansion. To this end, levels of several inflammatory markers (MCP-1, RANTES, IL-10, IL-17A, IL-12p, IFN-γ, IL-1ß, IL-8, and hs-CRP) and blood cells counts in plasma and/or serum of FTLD patients (N = 98) with or without the C9orf72 repeat expansion were analyzed. In addition, we evaluated whether the analyzed peripheral inflammatory markers correlated with disease progression or distinct clinical phenotypes under the heterogenous FTLD spectrum. Elevated levels of pro-inflammatory RANTES or MCP-1 and decreased levels of anti-inflammatory IL-10 were found to associate with Parkinsonism and a more rapid disease progression, indicated by longitudinal measurements of either MMSE or ADCS-ADL decline. These findings were observed in the total cohort in general, whereas the C9orf72 repeat expansion carriers showed only slight differences in IL-10 and hemoglobin levels compared to non-carriers. Furthermore, these C9orf72 repeat expansion-associated differences were observed mostly in male subjects. The females in general showed elevated levels of several pro-inflammatory markers compared to males regardless of the C9orf72 genotype. Our study suggests that pro-inflammatory changes observed in the early symptomatic phase of FTLD are associated with distinct clinical profiles and a more rapid disease progression, and that the C9orf72 repeat expansion and gender may also affect the inflammatory profile in FTLD.


Asunto(s)
Proteína C9orf72/genética , Progresión de la Enfermedad , Degeneración Lobar Frontotemporal/sangre , Degeneración Lobar Frontotemporal/fisiopatología , Inflamación/sangre , Anciano , Expansión de las Repeticiones de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales
9.
Fluids Barriers CNS ; 17(1): 57, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32933532

RESUMEN

BACKGROUND: The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. METHODS: Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. RESULTS: Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). CONCLUSIONS: Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.


Asunto(s)
Diabetes Mellitus/epidemiología , Hidrocéfalo Normotenso/epidemiología , Hidrocéfalo Normotenso/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Comorbilidad , Depresión/epidemiología , Familia , Femenino , Cardiopatías/epidemiología , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad
10.
Neurosurgery ; 84(4): 883-889, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29741669

RESUMEN

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and potentially treatable neurodegenerative disease affecting elderly people, characterized by gait impairment and ventricular enlargement in brain imaging. Similar findings are seen in some patients with schizophrenia (SCZ). OBJECTIVE: To determine the prevalence of SCZ among patients suffering from probable or possible iNPH and the specific effects of comorbid SCZ on the outcome of the cerebrospinal fluid (CSF) shunting. METHODS: All medical records of the 521 iNPH patients in the NPH registry were retrospectively analyzed from 1991 until 2017. The prevalence of comorbidity of SCZ was determined and compared to that of general aged (≥65 yr) population in Finland. RESULTS: We identified a total of 16 (3.1%) iNPH patients suffering from comorbid SCZ. The prevalence of SCZ among the iNPH patients was significantly higher compared to the general population (3.1% vs 0.9%, P < .001). All iNPH patients with comorbid SCZ were CSF shunted and 12 (75%) had a clinically verified shunt response 3 to 12 mo after the procedure. The CSF shunt response rate did not differ between patients with and without comorbid SCZ. CONCLUSION: SCZ seems to occur 3 times more frequently among iNPH patients compared to the general aged population in Finland. The outcome of the treatment was not affected by comorbid SCZ and therefore iNPH patients suffering from comorbid SCZ should not be left untreated. These results merit validation in other populations. In addition, further research towards the potential connection between these chronic conditions is warranted.


Asunto(s)
Hidrocéfalo Normotenso , Esquizofrenia , Anciano , Finlandia/epidemiología , Humanos , Hidrocéfalo Normotenso/complicaciones , Hidrocéfalo Normotenso/epidemiología , Prevalencia , Estudios Retrospectivos , Esquizofrenia/complicaciones , Esquizofrenia/epidemiología
11.
J Alzheimers Dis ; 66(2): 743-750, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30320585

RESUMEN

Recent studies have shown an epidemiological and immunological association between bullous pemphigoid (BP) and several neurological or psychiatric diseases. Here, our aim was for the first time to specify whether an association exists between BP and frontotemporal lobar degeneration (FTLD). Medical histories of FTLD patients (N = 196) were screened for clinical comorbidity, and BP180 and BP230 autoantibodies were analyzed in the sera of FTLD patients (N = 70, including 24 C9orf72 repeat expansion carriers) by BP180-NC16A-ELISA and BP230-ELISA. One FTLD patient (C9orf72 repeat expansion carrier) had a comorbid diagnosis of BP. Increased levels of serum BP180 autoantibodies (cutoff value >9 U/ml) were detected more often in FTLD patients (10.0%) than in controls (4.9%). Moreover, elevated levels of both BP180 and BP230 autoantibodies were found more often in C9orf72 repeat expansion-carrying FTLD than non-carrying patients or controls. However, none of these differences reached a statistical significance likely due to our limited cohort size. In conclusion, our findings suggest that subset of FTLD patients especially with the C9orf72 repeat expansion may have an immunological association with BP.


Asunto(s)
Degeneración Lobar Frontotemporal/epidemiología , Penfigoide Ampolloso/epidemiología , Anciano , Autoanticuerpos/sangre , Autoantígenos/inmunología , Proteína C9orf72/genética , Expansión de las Repeticiones de ADN/genética , Distonina/inmunología , Femenino , Finlandia/epidemiología , Degeneración Lobar Frontotemporal/sangre , Degeneración Lobar Frontotemporal/genética , Humanos , Masculino , Persona de Mediana Edad , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/sangre , Penfigoide Ampolloso/genética , Colágeno Tipo XVII
12.
Neurol Genet ; 4(6): e291, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30584596

RESUMEN

OBJECTIVE: To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. METHODS: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. RESULTS: The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. CONCLUSIONS: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.

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