AUTHOR=Akinyemi Rufus O. , Allan Louise M. , Oakley Arthur , Kalaria Rajesh N. 

TITLE=Hippocampal Neurodegenerative Pathology in Post-stroke Dementia Compared to Other Dementias and Aging Controls

JOURNAL=Frontiers in Neuroscience

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2017.00717

DOI=10.3389/fnins.2017.00717

ISSN=1662-453X

ABSTRACT=<p>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 (<italic>n</italic> = 12), vascular dementia, VaD (17), post-stroke demented, PSD (<italic>n</italic> = 15), and post-stroke non-demented, PSND (<italic>n</italic> = 23), Alzheimer's disease, AD (<italic>n</italic> = 14), and mixed AD and vascular dementia, AD_VAD (<italic>n</italic> = 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 (<italic>p</italic> &lt; 0.05). <italic>APOE</italic> ε4 allele positivity was associated with higher expression of amyloid and tau pathology in the subiculum and entorhinal cortex of post-stroke cases (<italic>p</italic> &lt; 0.05). Comparison between PSND and PSD revealed higher total Aβ immunoreactivity in PSND compared to PSD in the CA1, subiculum and entorhinal cortex (<italic>p</italic> &lt; 0.05) but no differences between PSND and PSD in Aβ-42, Aβ-40, soluble Aβ or tau immunoreactivities (<italic>p</italic> &gt; 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 (<italic>p</italic> &lt; 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.</p>