While cytoplasmic aggregation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia, how aggregates form and what drives its nuclear clearance have not been determined.
Whereas wild-type UBQLN2 accumulates in intraneuronal deposits in several common age-related neurodegenerative diseases, mutations in the gene encoding this protein result in X-linked amyotrophic lateral sclerosis/frontotemporal dementia associated with TDP43 accumulation.
We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2), which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease.
We used next generation sequencing of the whole gene (n = 700), exon 2 Sanger sequencing (n = 2634), p.R47H genotyping (n = 3518), and genome wide association study imputation (n = 13,048) to determine whether TREM2 variants are risk factors or phenotypic modifiers in patients with AD (n = 1002), frontotemporal dementia (n = 358), sporadic (n = 2500), and variant (n = 115) Creutzfeldt-Jakob disease (CJD).
We used microtubule-associated protein tau (MAPT) exon 10, whose missplicing causes frontotemporal dementia, to test the reporter in screening libraries of known bioactive compounds.
We suggest that the presence of the BDNF Val allele in itself and in combination with the ApoE epsilon4 allele can be risk factors for AD, and the results indicate a synergistic effect of the 2 polymorphisms on DLB and PiD risk.
We suggest that the presence of the BDNF Val allele in itself and in combination with the ApoE epsilon4 allele can be risk factors for AD, and the results indicate a synergistic effect of the 2 polymorphisms on DLB and PiD risk.
We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U.
We subsequently performed a genome-wide association study and identified the TMEM106B and GRN gene loci, previously associated with frontotemporal dementia, as determinants of Δ-aging in the cerebral cortex with genome-wide significance.
We subsequently performed a genome-wide association study and identified the TMEM106B and GRN gene loci, previously associated with frontotemporal dementia, as determinants of Δ-aging in the cerebral cortex with genome-wide significance.
We sought to determine the contribution of C9orf72 repeat expansions, recently discovered as a cause of frontotemporal dementia and amyotrophic lateral sclerosis, in a large number of Parkinson's disease patients.
We report the novel p.P397SMAPT variant in eight subjects from five apparently nonrelated families suffering from frontotemporal dementia with autosomal dominant pattern of inheritance.
We report on a 55-year old woman with frontotemporal dementia and a family history of FTDP-17 in whom we found a novel E12 (Glu342Val) tau gene mutation, prominent frontotemporal neuron loss, intracytoplasmic tau aggregates, paired helical tau filaments, increased 4R tau messenger RNA, increased 4R tau without E2 or E3 inserts, decreased 4R tau with these inserts, and a 4R:3R tau ratio greater than 1 in gray and white matter.
We report association of APOE and TOMM40 with behavioural variant frontotemporal dementia, and ARHGAP35 and SERPINA1 with progressive non-fluent aphasia.
We report a case of frontotemporal dementia caused by a novel MAPT mutation (Q351R) with a remarkably long amnestic presentation mimicking familial Alzheimer's disease.
We recently reported that dysfunction of ESCRT-III, either by depletion of its essential subunit mSnf7-2 or by expression of a mutant CHMP2B protein associated with frontotemporal dementia linked to chromosome 3 (FTD3), caused autophagosome accumulation and dendritic retraction before neurodegeneration in cultured mature cortical neurons.
We present the case that preventing the misfolding of TDP-43 and/or enhancing its clearance represents the most important target for effectively treating ALS and frontotemporal dementia.
We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K mutation in the MAPT gene from the family known as pallido-ponto-nigral degeneration (PPND).
We performed a genetic screen for regulators of RAN translation and identified small ribosomal protein subunit 25 (RPS25), presenting a potential therapeutic target for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia and other neurodegenerative diseases caused by nucleotide repeat expansions.