Grothe, Michel J.Moscoso, AlexisSilva-Rodríguez, JesúsLange, CatharinaNho, KwangsikSaykin, Andrew J.Nelson, Peter T.Schöll, MichaelBuchert, RalphTeipel, StefanAlzheimer’s Disease Neuroimaging Initiative2024-07-152024-07-152023Grothe MJ, Moscoso A, Silva-Rodríguez J, et al. Differential diagnosis of amnestic dementia patients based on an FDG-PET signature of autopsy-confirmed LATE-NC. Alzheimers Dement. 2023;19(4):1234-1244. doi:10.1002/alz.12763https://hdl.handle.net/1805/42208Introduction: Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is common in advanced age and can underlie a clinical presentation mimicking Alzheimer's disease (AD). We studied whether an autopsy-derived fluorodeoxyglucose positron emission tomography (FDG-PET) signature of LATE-NC provides clinical utility for differential diagnosis of amnestic dementia patients. Methods: Ante mortem FDG-PET patterns from autopsy-confirmed LATE-NC (N = 7) and AD (N = 23) patients were used to stratify an independent cohort of clinically diagnosed AD dementia patients (N = 242) based on individual FDG-PET profiles. Results: Autopsy-confirmed LATE-NC and AD groups showed markedly distinct temporo-limbic and temporo-parietal FDG-PET patterns, respectively. Clinically diagnosed AD dementia patients showing a LATE-NC-like FDG-PET pattern (N = 25, 10%) were significantly older, showed less abnormal AD biomarker levels, lower APOE ε4, and higher TMEM106B risk allele load. Clinically, they exhibited a more memory-predominant profile and a generally slower disease course. Discussion: An autopsy-derived temporo-limbic FDG-PET signature identifies older amnestic patients whose clinical, genetic, and molecular biomarker features are consistent with underlying LATE-NC.en-USPublisher PolicyTDP-43TMEM106BAmyloidApolipoprotein EAutopsyFluorodeoxyglucose positron emission tomographyHippocampal sclerosisLimbic age-related TDP-43 encephalopathyTauArticle