Platelets and Alzheimer's disease: Potential of APP as a biomarker

Platelets are the first peripheral source of amyloid precursor protein (APP). They possess the proteolytic machinery to produce A beta and fragments similar to those produced in neurons, and thus offer an ex-vivo model to study APP processing and changes associated with Alzheimer's disease (AD). Platelet process APP mostly through the alpha-secretase pathway to release soluble APP (sAPP). They produce small amounts of A beta, predominantly A beta 40 over A beta 42. sAPP and A beta are stored in alpha-granules and are released upon platelet activation by thrombin and collagen, and agents inducing platelet degranulation. A small proportion of full-length APP is present at the platelet surface and this increases by 3-fold upon platelet activation. Immunoblotting of platelet lysates detects APP as isoforms of 130 kDa and 106-110 kDa. The ratio of these of APP isoforms is significantly lower in patients with AD and mild cognitive impairment (MCI) than in healthy controls. This ratio follows a decrease that parallels cognitive decline and can predict conversion from MCI to AD. Alterations in the levels of alpha-secretase ADAM10 and in the enzymatic activities of alpha- and beta-secretase observed in platelets of patients with AD are consistent with increased processing through the amyloidogenic pathway. beta-APP cleaving enzyme activity is increased by 24% in platelet membranes of patients with MCI and by 17% in those with AD. Reports of changes in platelet APP expression with MCI and AD have been promising so far and merit further investigation as the search for blood biomarkers in AD, in particular at the prodromal stage, remains a priority and a challenge. (C) 2012 Baishideng. All rights reserved.