Progranulin mutations in clinical and neuropathological Alzheimer's disease.
Ontology highlight
ABSTRACT: Introduction
Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology.Methods
We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers.Results
Pathogenic GRN mutations were more frequent in all cohorts compared to the Genome Aggregation Database (gnomAD), but there was no evidence for association with AD. Pathogenic GRN carriers had significantly higher PHFtau tangle density adjusting for age, sex and APOE ε4 genotype. AD patients with rs5848 had higher frequencies of hippocampal sclerosis and TDP-43 deposits. Twenty-two rare, pathogenic GRN variants were observed in the family cohort.Discussion
GRN mutations in clinical and neuropathological AD increase the burden of tau-related brain pathology but show no specific association with β-amyloid load or AD.
SUBMITTER: Vardarajan BN
PROVIDER: S-EPMC9360185 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Progranulin mutations in clinical and neuropathological Alzheimer's disease.
Vardarajan Badri N BN Reyes-Dumeyer Dolly D Piriz Angel L AL Lantigua Rafael A RA Medrano Martin M Rivera Diones D Jiménez-Velázquez Ivonne Z IZ Martin Eden E Pericak-Vance Margaret A MA Bush William W Farrer Lindsay L Haines Jonathan L JL Wang Li-San LS Leung Yuk Yee YY Schellenberg Gerard G Kukull Walter W De Jager Philip P Bennett David A DA Schneider Julie A JA Mayeux Richard R
Alzheimer's & dementia : the journal of the Alzheimer's Association 20220209 12
<h4>Introduction</h4>Progranulin (GRN) mutations occur in frontotemporal lobar degeneration (FTLD) and in Alzheimer's disease (AD), often with TDP-43 pathology.<h4>Methods</h4>We determined the frequency of rs5848 and rare, pathogenic GRN mutations in two autopsy and one family cohort. We compared Braak stage, β-amyloid load, hyperphosphorylated tau (PHFtau) tangle density and TDP-43 pathology in GRN carriers and non-carriers.<h4>Results</h4>Pathogenic GRN mutations were more frequent in all coh ...[more]
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