Examining the Effects of a blood Glucose Rescue on Alzheimer's Disease-related Pathology in Hyperglycemic Mice

Document Type

Article

Publication Date

12-1-2021

Publication Title

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Volume

17

First page number:

e057639

Abstract

BACKGROUND: Diabetes Mellitus is a major risk factor for Alzheimer's disease (AD). Hyperglycemia is the primary characteristic of diabetes. Hyperglycemia was induced in both young and aged mice. Following a incubation period, a hyperglycemic rescue was introduced to lower hyperglycemia, and to determine if hyperglycemia itself, or neuroinflammation as a result of hyperglycemia, increased AD pathology (i.e., hyperphosphorylated tau). METHOD: Young (7 month old; N=24) and aged (18 month old; N=24) C57BL/6J (wildtype) mice were injected with a low and staggered dose of streptozotocin (STZ) to induce sustained hyperglycemia, seen in late-stage type II diabetes; a major non-genetic risk factor for Alzheimer's disease (AD). After a 9 week incubation period of hyperglycemia (e.g., +250mg/dl), a group of mice were treated with Phloridzin (PZ) - a drug that lowers hyperglycemia by preventing renal and intestine glucose uptake - to determine if hyperglycemia itself, or neuroinflammation as a result of hyperglycemia, increases AD pathology (e.g. hyperphosphorylated tau). RESULT: STZ increased hyperglycemia levels; PZ lowered hyperglycemia levels. Both young and aged STZ, PZ, and STZ+PZ mice showed significantly increased levels of P-S396-tau/total tau compared to controls. CONCLUSION: Fluctuating blood glucose levels may increase Alzheimer's disease-related pathology (e.g., hyperphosphorylated tau); a potential mechanism by which diabetes confers increased risk for developing AD.

Disciplines

Endocrinology, Diabetes, and Metabolism | Medical Pathology | Neurology

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