Genetic screening in early-onset dementia patients with unclear phenotype: relevance for clinical diagnosis.

Genetic screening in early-onset dementia patients with unclear phenotype: relevance for clinical diagnosis. Neurobiol Aging. 2018 May 09;: Authors: Perrone F, Cacace R, Van Mossevelde S, Van den Bossche T, De Deyn PP, Cras P, Engelborghs S, van der Zee J, Van Broeckhoven C Abstract In a prospective study of dementia in Flanders (Belgium), we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal genes linked to neurodegenerative brain diseases. In this group, the onset or inclusion age was 59.9 ± 8.2 years and 27.4% had a positive family history. We used a panel of 16 major genes linked to Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and prion diseases. In addition, we tested for the presence of a pathogenic C9orf72 repeat expansion. We identified 13 rare variants in 15 patients, including a carrier of variants in 2 different genes. Six patients (2.84%), carried a mutation in a Mendelian causal gene, that is, APP, MAPT, SOD1, TBK1, and C9orf72. In the other 7 patients, 7 variants were of uncertain significance, including a frameshift mutation in PSEN2, p.G359Lfs*74, in 2 patients sharing a common haplotype, and in LRRK2, p.L2063fs*. Expression studies showed reduced PSEN2 and a near complete lo...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research

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Conclusion: The complex molecular underpinnings of these disorders are currently elusive. Despite heterogeneous clinical and pathological expressions, common features have been recognized in many NDs which provide evidence of their convergence. PMID: 29755292 [PubMed]
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research
Authors: Liu X, Jiao B, Zhang W, Xiao T, Hou L, Pan C, Tang B, Shen L Abstract Recently, the coiled‑coil‑helix‑coiled‑coil‑helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Abstract Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These disease include Alzheimer's disease the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson's, Huntington's, Friedreich's ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the developm...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
Publication date: May 2018 Source:Neurochemistry International, Volume 115 Author(s): Zhihui Zhu, Georg Reiser Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding ...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Authors: Tae WS, Ham BJ, Pyun SB, Kang SH, Kim BJ Abstract Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relative...
Source: Journal of Clinical Neurology - Category: Neurology Tags: J Clin Neurol Source Type: research
In conclusion, the present study demonstrated that TIGIT is a prominent negative immune regulator involved in immunosenescence. This novel finding is highly significant, as targeting TIGIT might be an effective strategy to improve the immune response and decrease age-related comorbidities. Delivery of Extracellular Vesicles as a Potential Basis for Therapies https://www.fightaging.org/archives/2018/01/delivery-of-extracellular-vesicles-as-a-potential-basis-for-therapies/ Here I'll point out a readable open access review paper on the potential use of extracellular vesicles as a basis for therapy: harveste...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We have ascertained two families affected with familial amyotrophic lateral sclerosis (ALS) in which they both carry a hexanucleotide repeat expansion in the C9orf72 gene, specifically in individuals who also presented with frontotemporal dementia (FTD) or behavioral variant FTD (bvFTD). While some reports attribute this phenotypic heterogeneity to the C9orf72 expansion alone, we screened for additional genetic variation in known ALS‐FTD genes that may also contribute to or modify the phenotypes. We performed genetic testing consisting of C9orf72 hexanucleotide expansion, ATXN2 polyglutamine (polyQ) expansion, and target...
Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - Category: Genetics & Stem Cells Authors: Tags: RESEARCH ARTICLE Source Type: research
Conclusions: Familial aggregation of ALS and other neurodegenerative diseases implies a shared etiopathogenesis among all neurodegenerative diseases. The increased risk of psychiatric disorders among patients with ALS and their children might be attributable to nonmotor symptoms of ALS and severe stress response toward the diagnosis.
Source: Neurology - Category: Neurology Authors: Tags: Amyotrophic lateral sclerosis, All Psychiatric disorders, All Cognitive Disorders/Dementia, All epidemiology ARTICLE Source Type: research
Traynor BJ, Chia R, Chung SJ, International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium, Hardy JA, Brice A, Wood NW, Houlden H, Shulman JM, Morris HR, Gasser T, Krüger R, Heutink P, Sharma M, Simón-Sánchez J, Nalls MA, Singleton AB, Scholz SW Abstract Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurode...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type ...
Source: BMJ Open - Category: Journals (General) Authors: Tags: Open access, Epidemiology, Neurology, Pharmacology and therapeutics Protocol Source Type: research
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