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Platelet APP‐ratio correlates with CSF levels of Aβ1‐42 in Alzheimer’s disease patients
Author(s) -
Sarno Tamires Alves,
Talib Leda Leme,
Joaquim Helena Passarelli Giroud,
Radanovic Marcia,
de França Bram Jessyka Maria,
Gattaz Wagner Farid,
Forlenza Orestes Vicente
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043212
Subject(s) - platelet , cerebrospinal fluid , medicine , dementia , amyloid precursor protein , alzheimer's disease , endocrinology , antibody , immunology , disease , gastroenterology
Background The cerebrospinal fluid (CSF) is reputed as the best humoral matrix to address Alzheimer´s disease (AD) biomarkers. AD‐related CSF biomarkers are largely related to intracerebral amyloidosis, and have proved useful for diagnostic purposes and prediction of dementia in high‐risk populations. Lower CSF concentrations of Aβ1‐42 have been consistently reported in AD. However, results with peripheral biomarkers have so far yielded less consistent results. Platelets are the main peripheral source of amyloid precursor protein (APP) and contain the enzymatic machinery required for its proteolytic metabolism. Previous studies have shown that platelet APP ratio (130/110 kDa sAPP) is reduced in AD. Method We enrolled 66 older adults (26 with AD and 40 cognitively unimpaired subjects). The expression of 110‐ and 130kDA secreted APP peptides (sAPP) was determined in platelets by Western blotting using 22C11 monoclonal antibody, to determine APP ratio (rAPP). CSF concentrations of Aβ1‐42 were determined by a multiplexed method using commercial kits (Innobia AlzBio3). Result There were no statistically significant differences in age (p=0.67) or gender distribution (χ 2 =0.155; p=0.69) across groups. Compared to controls, AD patients had lower mean platelet rAPP (AD: 1.26, SD0.5; controls: 2.07, SD0.93; p<0.001) and CSF Aβ1‐42 concentrations (AD: 319.04, SD146.7; controls: 450.84, SD 109.9; p=0.001). We also found positive correlations between platelet rAPP and CSF Aβ1‐42 (Spearman’s Rho=0.40; p=0.01). Conclusion Our findings confirm that platelet rAPP and CSF Aβ1‐42 are reduced in AD. We further show that these two parameters are correlated, indicating that platelet rAPP may be regarded as a surrogate marker of intracerebral accumulation of amyloid‐beta.