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P3‐207: ARE VISUAL HALLUCINATIONS IN ALZHEIMER'S DISEASE A RESULT OF HYPOPERFUSION OF VISUAL PROCESSING AREAS IN THE OCCIPITAL CORTEX?
Author(s) -
Sinclair Lindsey I.,
Darreh-Shori Taher,
Mandagere Vinay,
Love Seth
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1566
Subject(s) - dementia with lewy bodies , lewy body , occipital lobe , visual cortex , pathology , visual hallucination , psychology , dementia , medicine , cortex (anatomy) , perfusion , alzheimer's disease , neuroscience , disease , audiology
amyloidogenesis promotes neoangiogenesis leading to increased BBB permeability and hypervascularization, subsequently causing cognitive decline. Recent studies, have examined the role Abeta plays in angiogenesis of the neurovasculature and BBB and how it contributes to AD pathogenesis. It is noted that accumulation of Abeta in cerebral vasculature is associated with perturbations in the blood-brain barrier (BBB) [1, 2], coinciding with onset of cognitive impairment. While it was originally hypothesized that accumulation of Abeta and subsequent disruption of the BBB was due to impaired clearance of Abeta from the brain, recent studies have implicated Amyloidgenesis in angiogenesis. It has also been demonstrated that BBB integrity is compromised early on in Tg2576 AD mice[2-4] and this BBB disruption precedes development of senile plaques. Furthermore, decreased cerebrovascular integrity (i.e. tight junction (TJ) integrity) in Tg2576 mice was found in conjunction with markers of angiogenesis but not apoptosis[2]. These data suggests that Abeta itself is vasculotropic and that amyloidogenic triggered hypervascularity may be the basis for BBB disruption in AD[2] and suggests a new mode for treating AD, where modulating angiogenesis may help to repair damage in the AD brain. Methods: Tg2576 mice and Wildtype littermates (age1⁄410 months;n1⁄410) were treated with small molecule antiangiogenic drug, Axitinib, for one month. Behavioral analysis was carried out to test various aspects of memory; associative, spatial awareness, working and reference memory. Animals were sacrificed and brains were harvested for molecular (western blotting) and histological analysis to assess various markers of AD pathology. Results: Post treatment with small molecule antiangiogenic drug, there is significant cognitive improvement in the AD mouse model. There was a reduction in the overall amyloid load, actively sprouting angiogenic vessles and BBB permeability. Conclusions:Modulation of the pathogenic angiogenesis observed in the AD brain can alleviate AD pathology in Tg2576 mice. This indicates a novel therapeutic intervention towards Alzheimer’s disease.