Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimer’s disease and Parkinson’s disease dementia
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INTRODUCTION
Tau pathology typically occurs in Alzheimeŕs disease (AD), however is also frequently present in Parkinsońs disease dementia (PDD) and Dementia with Lewy Bodies (DLB), yet its disease-specific signature is unclear.
METHODS
Five tau, amyloid-β, α-synuclein and neuronal markers were analysed across hippocampal subfields in non-demented controls (CTLs), AD, PDD and DLB using multiplex immunohistochemistry, single-tangle classification and confocal imaging.
RESULTS
AT8, pTau217, and GT38 were predominatly detected in AD, while pS422 was enriched in PDD and pS396 showed a region- and disease-specific pattern. DLB resembled AD in subregional tau distribution. Tau marker correlation were different comparing AD, PDD and CTL. Single-tangle analyses revealed disease-specific immunophenotypes but conserved mature intra-tangle epitope organisation. Distinct tau signatures were associated with inhibitory interneuron vulnerability, while regional tau co-occurrence with amyloid-β and α-synuclein remained conserved.
DISCUSSION
Disease-specific tau signatures vary across hippocampal subregions and neuronal populations, implicating the contribution of regional and cell-specific factors beyond pathology burden.
