%0 Journal Article %J J Alzheimers Dis %D 2019 %T A Fragment of S38AA is a Novel Plasma Biomarker of Alzheimer's Disease. %A Hashimoto, Masakazu %A Yamazaki, Akira %A Ohno, Atsushi %A Kimura, Toru %A Winblad, Bengt %A Tjernberg, Lars O %X

Alzheimer's disease (AD) is a progressive neurodegenerative disease without a cure. The pathological process starts decades before clinical onset, and thus clinical trials of drugs aimed at treating AD should start at a presymptomatic stage. Therefore, it is critical to diagnose AD at an early stage. Tau, phosphorylated tau, and amyloid-β peptide (Aβ) in cerebrospinal fluid (CSF), and positron emission tomography (PET) imaging of Aβ or tau accumulation are supportive biomarkers for AD diagnosis, but there is no reliable presymptomatic diagnostic marker. Since CSF sampling is invasive, and PET imaging is expensive and available only at specialized centers, a reliable blood biomarker has long been sought for. Here we describe a novel extramembrane fragment from solute carrier family 38 member 10 (SLC38A10, S38AA) that we found to be decreased in pyramidal neurons in AD cases by proteomics and immunohistochemical analysis. We detected a S38AA fragment in CSF and found the levels to correlate with severity of AD and APOE genotype. Importantly, the plasma levels of the fragment also showed a significant correlation with Mini-Mental State Examination scores in AD. Moreover, plasma from other neurodegenerative disease was analyzed and the fragment was found to be increased specifically in AD. Interestingly, the fragment is detected in mouse, rat, and monkey, and increases in amyloid precursor protein transgenic mice as the AD-like pathology progresses. We propose that the S38AA fragment in plasma could be a novel quantitative diagnostic marker for AD and potentially a marker of disease progression in AD.

%B J Alzheimers Dis %V 71 %P 1163-1174 %8 2019 Oct 15 %G eng %N 4 %R 10.3233/JAD-190700