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Decreased platelet APP isoform ratios in autosomal dominant Alzheimer’s disease: Baseline data from a DIAN cohort subset
journal contribution
posted on 2023-01-31, 04:59 authored by P Chatterjee, Veer GuptaVeer Gupta, A M Fagan, M S Jasielec, C Xiong, H R Sohrabi, S Dhaliwal, K Taddei, P Bourgeat, B M Brown, T Benzinger, R J Bateman, J C Morris, R N MartinsIntroduction: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer’s disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. Methods: APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson’s correlation coefficient (r). Results: APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). Conclusion: APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.
History
Journal
Current Alzheimer ResearchVolume
12Pagination
157 - 164Publisher DOI
ISSN
1567-2050eISSN
1875-5828Publication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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No categories selectedKeywords
Science & TechnologyLife Sciences & BiomedicineClinical NeurologyNeurosciencesNeurosciences & NeurologyAlzheimer's diseaseamyloid precursor proteinbiomarkersneuropsychological testsPittsburgh compound BplateletsMILD COGNITIVE IMPAIRMENTPERIPHERAL MARKERPRESENILIN-1 MUTATIONMEMBRANE-FLUIDITYADIDENTIFICATIONEXPRESSIONDominantly Inherited Alzheimer Network
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