Blood cell markers in Alzheimer Disease: Amyloid Precursor Protein form ratio in platelets

Abstract

A correct clinical diagnosis in the early stage of Alzheimer disease (AD) is mandatory given the current available treatment with acetylcholine esterase inhibitors. Moreover, a early to preclinical diagnosis would allow to identify patients eligible for future diseasemodifying therapies.In the last ten years, we have focused our attention on peripheral markers, evaluating the role of platelet Amyloid Precursor Protein (APP) forms as a reliable tool for AD diagnosis since preclinical stages. APP is the key player in AD pathogenesis, and platelets contain all the enzymatic machinery to its processing, thus being the ideal candidate where to study AD pathogenetic mechanisms.In this review, we summarise the published data regarding the usefulness of platelet APP form ratio in the diagnosis of early AD. Approaches combining APP form ratio along with neuroimaging markers show the promise to accurately identify AD, even in the pre-symptomatic stage.

ADAM10 as a Biomarker for Alzheimer’s Disease: A Study with Brazilian Elderly

“…Among the peripheral tissues, the platelets present the highest APP expression levels [10]. The platelets store and liberate neurotransmitters and carry appropriate transporters and receptors, normally expressed by neuronal cells [11].…”

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

“…In the periphery, platelets express high levels of APP and an altered pattern of APP isoforms (130 -110 -106 kDa) has been reported in the platelets of AD patients [90][91][92][93] . The APP ratio in MCI and AD, but not in other dementias, is reduced compared to controls with a sensitivity and specificity between 70% and 95%, correlating with AD severity [90][91][92] . Information about plateletgenerated APP and its contribution to AD pathology is still lacking and the potential of the APP ratio as a biomarker is still unclear.…”

“…BACE cleaves APP and releases a large N-terminal fragment (sAPPβ). The membrane-anchored frag- [73,75] Decreased [65] β-amyloid (Aβ) Decreased [45,46] No difference [79][80][81][82] No difference [47] Aβ1- 40 No difference [24] No difference [83] Increased [84] Decreased [85] Aβ1- 42 Decreased [24] Increased [83] -Aβ1-42/Aβ1-40 ratio Decreased [48] No difference [83] Decreased [78,84,86] APP ratio --Decreased [90][91][92][93] Ubiquitin Increased [24] No difference [148] BACE1 Increased [67] --Cholesterol -Decreased [94,95] Increased [96][97][98] 24S-hydroxycholesterol Increased [102] No difference [103] Decreased [104] Homocysteine -Increased [106,107,109] Epidermal growth factor -Decreased [111] Decreased [93] Increased [112] Glial cell line-derived growth factor -Decreased [111] No difference …”

Platelets in psychiatric disorders

“…Neuropathology includes β-amyloid (Aβ) plaques in brain and vessels, neurofibrilary tangles with hyperphosphorylated tau protein [6] , inflammation [7] and cerebrovascular damage [8] . Platelets are an interesting tool to study the cellular mechanisms of AD, because they contain highest levels of the precursor of β-amyloid (APP) compared to all peripheral tissues [9][10][11][12] and all three isoforms of APP (130, 110 and 106 kDa) are detectable in platelets [9,13] . Full length APP is cleaved by a Ca 2+ dependent cysteine protease during platelet activation [10] and APP processing is altered in patients suffering from AD [14] resulted in a reduced ratio between the 130 kDa and 106-110 kDa APP isoform [11] , suggesting that APP ratios in platelets could be a biomarker for AD.…”