Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimers disease and Parkinsons disease dementia

Schreiner, S.; Miranda de la Maza, M.; Hammer, G. P.; Jeannelle, F.; Darricau, M.; Mirault, D.; Mechawar, N.; Netherlands Brain Bank,; Mittelbronn, M.; Bouvier, D. S.

doi:10.64898/2026.08.13.744594

bioRxiv · 10.64898/2026.08.13.744594

Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimers disease and Parkinsons disease dementia

Schreiner, S.·Miranda de la Maza, M.·Hammer, G. P.·Jeannelle, F.·Darricau, M.·Mirault, D.·Mechawar, N.·Netherlands Brain Bank,·Mittelbronn, M.·Bouvier, D. S.

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Abstract

Structured AbstractINTRODUCTION Tau pathology typically occurs in Alzheime[r]s disease (AD), however is also frequently present in Parkinso[n]s disease dementia (PDD) and Dementia with Lewy Bodies (DLB), yet its disease-specific signature is unclear. METHODSFive tau, amyloid-{beta}, -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. RESULTSAT8, 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-{beta} and -synuclein remained conserved. DISCUSSIONDisease-specific tau signatures vary across hippocampal subregions and neuronal populations, implicating the contribution of regional and cell-specific factors beyond pathology burden.

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Schreiner, S., Miranda de la Maza, M., Hammer, G. P., Jeannelle, F., Darricau, M., Mirault, D., Mechawar, N., Netherlands Brain Bank,, Mittelbronn, M., Bouvier, D. S.. 2026-08-22. Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimers disease and Parkinsons disease dementia. https://doi.org/10.64898/2026.08.13.744594

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