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Hippocampal neurodegenerative pathology in post-stroke dementia compared to other dementias and aging controls

Lookup NU author(s): Dr Rufus Akinyemi, Dr Louise Allan, Arthur Oakley, Professor Raj KalariaORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2017 Akinyemi, Allan, Oakley and Kalaria. Neuroimaging evidence from older stroke survivors in Nigeria and Northeast England showed medial temporal lobe atrophy (MTLA) to be independently associated with post-stroke cognitive impairment and dementia. Given the hypothesis ascribing MTLA to neurodegenerative processes, we assessed Alzheimer pathology in the hippocampal formation and entorhinal cortex of autopsied brains from of post-stroke demented and non-demented subjects in comparison with controls and other dementias. We quantified markers of amyloid β (total Aβ, Aβ-40, Aβ-42, and soluble Aβ) and hyperphosphorylated tau in the hippocampal formation and entorhinal cortex of 94 subjects consisting of normal controls (n = 12), vascular dementia, VaD (17), post-stroke demented, PSD (n = 15), and post-stroke non-demented, PSND (n = 23), Alzheimer's disease, AD (n = 14), and mixed AD and vascular dementia, AD_VAD (n = 13) using immunohistochemical techniques. We found differential expression of amyloid and tau across the disease groups, and across hippocampal sub-regions. Among amyloid markers, the pattern of Aβ-42 immunoreactivity was similar to that of total Aβ. Tau immunoreactivity showed highest expression in the AD and mixed AD and vascular dementia, AD_VaD, which was higher than in control, post - stroke and VaD groups (p < 0.05). APOE ε4 allele positivity was associated with higher expression of amyloid and tau pathology in the subiculum and entorhinal cortex of post-stroke cases (p < 0.05). Comparison between PSND and PSD revealed higher total Aβ immunoreactivity in PSND compared to PSD in the CA1, subiculum and entorhinal cortex (p < 0.05) but no differences between PSND and PSD in Aβ-42, Aβ-40, soluble Aβ or tau immunoreactivities (p > 0.05). Correlation of MMSE and CAMCOG scores with AD pathological measures showed lack of correlation with amyloid species although tau immunoreactivity demonstrated correlation with memory scores (p < 0.05). Our findings suggest hippocampal AD pathology does not necessarily differ between demented and non-demented post-stroke subjects. The dissociation of cognitive performance with hippocampal AD pathological burden suggests more dominant roles for non-Alzheimer neurodegenerative and / or other non-neurodegenerative substrates for dementia following stroke.

Publication metadata

Author(s): Akinyemi RO, Allan LM, Oakley A, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Frontiers in Neuroscience

Year: 2017

Volume: 11

Online publication date: 19/12/2017

Acceptance date: 08/12/2017

Date deposited: 11/01/2018

ISSN (print): 1662-4548

ISSN (electronic): 1662-453X

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fnins.2017.00717

DOI: 10.3389/fnins.2017.00717

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