Authors
Preeti Sharma, Rajath Devappa, Sivaprakasam R Saroja
Published in
bioRxiv : the preprint server for biology. Sep 08, 2026. Epub Sep 08, 2026.
Abstract
Alzheimer disease neuropathologic change (ADNC) does not fully explain clinical severity, suggesting important contributions from coexisting pathologies. We examined major co-pathologies in a multicenter autopsy cohort, focusing on hippocampal/medial temporal sclerosis (HS/MTL sclerosis), clinical severity, regional TDP-43 topography, clinical status near death, and gross hippocampal atrophy. We analyzed longitudinal clinical and neuropathology data from the National Alzheimer's Coordinating Center autopsy cohort. Form-specific definitions harmonized AD pathology, major co-pathologies, HS/MTL sclerosis, and regional TDP-43 findings across neuropathology versions 8-10. HS/MTL sclerosis was present in 13.0% of assessed AD cases and was associated with greater CDR® Dementia Staging Instrument sum-of-boxes severity in non-AD (odds ratio [OR], 4.93; 95% confidence interval [CI], 3.66-6.63) and AD strata (OR, 2.56; 95% CI, 2.15-3.04). In version 10, HS/MTL sclerosis was associated with higher regional TDP-43 topography (OR, 6.54; 95% CI, 3.88-11.02) and greater gross hippocampal atrophy (OR, 6.43; 95% CI, 4.97-8.32). Among AD cases assessed within 2 years of death, HS-negative participants had greater odds of non-dementia status than HS-positive participants (OR, 5.81; 95% CI, 2.80-12.06). HS/MTL sclerosis marked greater clinical severity in both AD and non-AD strata and co-occurred with regional TDP-43 involvement and hippocampal atrophy. Its absence identified a subset with intermediate/high AD pathology but no dementia near death. Clinical severity therefore cannot be inferred from ADNC alone.
PMID:
42818556
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.
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