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Media type:
E-Article
Title:
Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis
Contributor:
Stage, Eddie C.;
Svaldi, Diana;
Phillips, Meredith;
Canela, Victor Hugo;
Duran, Tugce;
Goukasian, Naira;
Risacher, Shannon L.;
Saykin, Andrew J.;
Apostolova, Liana G.
Published:
Springer Science and Business Media LLC, 2020
Published in:
Alzheimer's Research & Therapy, 12 (2020) 1
Language:
English
DOI:
10.1186/s13195-020-00647-w
ISSN:
1758-9193
Origination:
Footnote:
Description:
AbstractBackgroundA substantial number of patients clinically diagnosed with Alzheimer’s disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis.MethodsOne hundred and ten early-onset AD (EOAD), 121 EOnonAD, 364 late-onset AD (LOAD), and 175 LOnonAD mild cognitive impairment (MCI) and dementia (DEM) subjects were compared to 291 ADNI amyloid-negative control subjects using voxel-wise regression in SPM12 with cluster-level family-wise error correction at pFWE < 0.05). A subset of these subjects also received 18F-flortaucipir scans and allowed for analysis of global tau burden.ResultsAs expected, relative to LOAD, EOAD subjects showed more extensive neurodegeneration and tau deposition in AD-relevant regions. EOnonADMCI showed no significant neurodegeneration, while EOnonADDEM showed bilateral medial and lateral temporal, and temporoparietal hypometabolism. LOnonADMCI and LOnonADDEM showed diffuse brain atrophy and a fronto-temporo-parietal hypometabolic pattern. LOnonAD and EOnonAD subjects failed to show significant tau binding.ConclusionsLOnonAD subjects show a fronto-temporal neurodegenerative pattern in the absence of tau binding, which may represent underlying hippocampal sclerosis with TDP-43, also known as limbic-predominant age-related TDP-43 encephalopathy (LATE). The hypometabolic pattern observed in EOnonADDEM seems similar to the one observed in EOADMCI. Further investigation into the underlying etiology of EOnonAD is warranted.