P2‐079: Amylin Dyshomeostasis Disrupts White Matter Structural Integrity and Modulates Amyloid Composition and Pathology Distribution in Brains of Patients With Ad and Ad Rats
Year: 2019
Type: article
Abstract: Recent data shows that the brains of individuals with Alzheimer's disease (AD) contain deposits of amylin, an amyloidogenic peptide that makes up the pancreatic amyloid in type-2 diabetes. In the animal model of amylin dyshomeostasis (rats overexpressing human amylin in the pancreas - HIP rats), amylin accumulation in the brain white matter is associated with white matter injury. We hypothesize that amylin dyshomeostasis injures the brain white matter and modulates the amyloid composition and distribution within the grey matter in AD. Temporal lobe samples from non-diabetic familial Alzheimer's disease (fAD) patients with presenilin (n=20) or amyloid precursor protein mutations (n=7) and healthy individuals (n=12) were tested for brain amylin accumulation. Amylin-Aβ interaction and the anatomical distribution of the pathology were assessed by immunohistochemistry. To further test the hypothesis that amylin dyshomeostasis modulates AD pathology, we crossed TgF344-19 AD rats (which overexpress human APPSwe/PS1dE9 from a PrP promoter) with HIP rats. The newly generated ADHIP rats were compared with AD, HIP and wild-type littermates (males; n=10/group). Amylin-Aβ pathology in the brain was assessed with immunohistochemistry. In the brain of fAD patients, amylin has higher tendency to accumulate in the white matter compared to Aβ, suggesting that amylin preponderantly induces pathology in the brain white matter in fAD. In the brain grey matter, both independent amylin deposits and mixed amylin-Aβ plaques are found in fAD individuals. Similar to the pathology distribution observed in the brains of fAD patients, ADHIP and HIP rats (overexpressing human amylin in the pancreas) show a higher tendency of amylin accumulation in the brain white matter when compared to Aβ. Amylin deposits and amylin-Aβ mixed plaques are found in the grey matter of ADHIP brains. Amylin dyshomeostasis induces white matter pathology and modulates the amyloid composition in familial AD.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981034488