Abnormal platelet amyloid-β precursor protein metabolism in SAMP8 mice: Evidence for peripheral marker in Alzheimer's disease.

Senescence-accelerated mouse strains have proved to be an accelerated-aging model, which mimics numerous features with Alzheimer's disease (AD). Three, six, and nine-month senescence-accelerated resistant 1 and senescence-accelerated prone 8 (SAMP8) mice were used in the current study, to unravel potential mechanisms for dementia and explore new diagnostic approaches for AD. The amyloid-beta (A beta 40) and A beta 42 levels were elevated in hippocampi and platelets from SAMP8, along with a reduced alpha-secretase expression and an enhanced beta-secretase expression extent with age, compared to control mice. Furthermore, hippocampal A beta 40 and A beta 42 of SAMP8 were positively correlated with platelet of these mice with aging progression. In addition, beta-gamma-secretase-modulated proteolytic proceeding of amyloid precursor protein in platelet might work through the PI3K/Akt/GSK3 beta pathway. These results indicate that platelet could be a potential early marker in the periphery to study the age-correlative aggregation of the amyloid-beta peptide in patients with AD, while still requiring the considerable study.