-
Article
Open AccessAnnexin A11 aggregation in FTLD–TDP type C and related neurodegenerative disease proteinopathies
TAR DNA-binding protein 43 (TDP-43) is an RNA binding protein found within ribonucleoprotein granules tethered to lysosomes via annexin A11. TDP-43 protein forms inclusions in many neurodegenerative diseases i...
-
Article
Open AccessGenetic and phenotypic characterization of Parkinson’s disease at the clinic-wide level
Observational studies in Parkinson’s disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular an...
-
Article
Correction: APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
-
Article
Open AccessGlucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson’s disease
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are progressive neurodegenerative diseases characterized by the accumulation of misfolded α-synuclein in the form of Lewy pathology. While most case...
-
Article
Open AccessCorrection to: Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration
-
Article
Open AccessIsoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration
Frontotemporal lobar degeneration with MAPT pathogenic variants (FTLD-MAPT) has heterogeneous tau pathological inclusions postmortem, consisting of three-repeat (3R) or four-repeat (4R) tau isoforms, or a combina...
-
Article
TREM2 risk variants are associated with atypical Alzheimer’s disease
Alzheimer’s disease (AD) has multiple clinically and pathologically defined subtypes where the underlying causes of such heterogeneity are not well established. Rare TREM2 variants confer significantly increased ...
-
Article
Distinct characteristics of limbic-predominant age-related TDP-43 encephalopathy in Lewy body disease
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is characterized by the accumulation of TAR-DNA-binding protein 43 (TDP-43) aggregates in older adults. LATE coexists with Lewy body disease (LBD) as...
-
Article
Open AccessTau immunotherapy is associated with glial responses in FTLD-tau
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neuropathologic subtypes of frontotemporal lobar degeneration with tau inclusions (FTLD-tau), primary tauopathies in which intracell...
-
Article
ADNC-RS, a clinical-genetic risk score, predicts Alzheimer’s pathology in autopsy-confirmed Parkinson’s disease and Dementia with Lewy bodies
Growing evidence suggests overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD) pathophysiology in a subset of patients. Indeed, 50–80% of autopsy cases with a primary clinicopathological diagn...
-
Article
APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
Beta-amyloid deposition is a defining feature of Alzheimer’s disease (AD). How genetic risk factors, like APOE and TREM2, intersect with cellular responses to beta-amyloid in human tissues is not fully understood...
-
Article
Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-...
-
Article
Open AccessNeuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We ex...
-
Article
Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histo...
-
Article
Semi-automated quantification of C9orf72 expansion size reveals inverse correlation between hexanucleotide repeat number and disease duration in frontotemporal degeneration
We investigated whether chromosome 9 open reading frame 72 hexanucleotide repeat expansion (C9orf72 expansion) size in peripheral DNA was associated with clinical differences in frontotemporal degeneration (FTD) ...
-
Article
Open AccessCommon neuropathological features underlie distinct clinical presentations in three siblings with hereditary diffuse leukoencephalopathy with spheroids caused by CSF1R p.Arg782His
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) presents with a variety of clinical phenotypes including motor impairments such as gait dysfunction, rigidity, tremor and bradykinesia as well as co...
-
Article
Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier
C9orf72 promoter hypermethylation inhibits the accumulation of pathologies which have been postulated to be neurotoxic. We tested here whether C9orf72 hypermethylation is associated with prolonge...
-
Article
C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD
Hexanucleotide repeat expansions of C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal degeneration. The mutation is associated with reduced C9orf72 expression and the ...
-
Article
TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common...
