The search for a convenient procedure to detect one of the earliest signs of Alzheimer's disease: A systematic review of the prediction of brain amyloid status

Abstract

Introduction Convenient, cost‐effective tests for amyloid beta (Aβ) are needed to identify those at higher risk for developing Alzheimer's disease (AD). This systematic review evaluates recent models that predict dichotomous Aβ. (PROSPERO: CRD42020144734). Methods We searched Embase and identified 73 studies from 29,581 for review. We assessed study quality using established tools, extracted information, and reported results narratively. Results We identified few high‐quality studies due to concerns about Aβ determination and analytical issues. The most promising convenient, inexpensive classifiers consist of age, apolipoprotein E genotype, cognitive measures, and/or plasma Aβ. Plasma Aβ may be sufficient if pre‐analytical variables are standardized and scalable assays developed. Some models lowered costs associated with clinical trial recruitment or clinical screening. Discussion Conclusions about models are difficult due to study heterogeneity and quality. Promising prediction models used demographic, cognitive/neuropsychological, imaging, and plasma Aβ measures. Further studies using standardized Aβ determination, and improved model validation are required.

Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease

“…A substantial body of work now supports the ability of ultrasensitive plasma Aβ immunoassays and mass spectroscopy assays to accurately and detect brain Aβ (reviewed in Ashford et al 147 …”

“…A substantial body of work now supports the ability of ultrasensitive plasma A β immunoassays and mass spectroscopy assays to accurately and detect brain A β (reviewed in Ashford et al 147 ). Blood samples from ADNI CU and MCI participants were used to validate a model developed in the Swedish BioFinder study that combined age, APOE groups, a cognitive test (10 word list delayed recall), and plasma A β 42/40 to predict individual brain A β (AUC of 0.83).…”

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

“…Numerous studies in recent decades have focused on elucidating the etiopathology of AD, but its pathogenesis remains unclear, and no therapeutic strategy is available to cure this disease. Various molecular, biochemical, and cellular abnormalities such as cell loss, impaired energy metabolism, increased activation of signaling pathways, amyloid-β (Aβ) deposits, mitochondrial dysfunction, chronic oxidative stress, impaired energy metabolism, and DNA damage are involved in the pathogenesis of AD (Guo et al, 2020;Zhang Y. X. et al, 2020;Zolochevska and Taglialatela, 2020;Ashford et al, 2021). The neuropathological hallmarks of AD include the formation of senile plaques and neurofibrillary tangles in specific brain regions that lead to synaptic loss and neuronal death (Khan and Hegde, 2020;Mattsson-Carlgren et al, 2020;Konijnenberg et al, 2021).…”

Predicting Amyloid Positivity in Cognitively Unimpaired Older Adults

“…Many models require the performance of multiple neuropsychological examinations and evaluation of multiple genetic risk factors, structural MRIs, CSF, or blood-based biomarkers. 35…”