title: Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty.
abstract: Cognitive frailty (CF) overlaps with early neuropathological alterations associated with aging‑related major neurocognitive disorders, including Alzheimer's disease (AD). Fluid biomarkers for these pathological brain alterations allow for early diagnosis in the preclinical stages of AD, and for objective prognostic assessments in clinical intervention trials. These biomarkers may also be helpful in the screening of CF. The present study reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. The selection criteria for potentially suitable fluid biomarkers included: i) Frequent use in studies of fluid‑derived markers and ii) evidence of novel measurement techniques for fluid‑derived markers. The present study focused on studies that assessed these biomarkers in AD, mild cognitive impairment and non‑AD demented subjects. At present, widely used fluid biomarkers include cerebrospinal fluid (CSF), total tau, phosphorylated tau and amyloid‑β levels. With the development of novel measurement techniques and improvements in understanding regarding the mechanisms underlying aging‑related major neurocognitive disorders, numerous novel biomarkers associated with various aspects of AD neuropathology are being explored. These include specific measurements of Aβ oligomer or monomer forms, tau proteins in the peripheral plasma and CSF, and novel markers of synaptic dysfunction, neuronal damage and apoptosis, neuronal activity alteration, neuroinflammation, blood brain barrier dysfunction, oxidative stress, metabolites, mitochondrial function and aberrant lipid metabolism. The proposed panels of fluid biomarkers may be useful in the early diagnosis of AD, prediction of the progression of AD from preclinical stages to the dementia stage, and the differentiation of AD from non‑AD dementia. In combination with physical frailty, the present study surmised that these biomarkers may also be used as biomarkers for CF, thus contribute to discovering causes and informing interventions for cognitive impairment in individuals with CF.
authors: Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Department of Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China.
authors: Qingwei
authors: Q
authors: Ruan
authors: Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, I‑71013 Foggia, Italy.
authors: Grazia
authors: G
authors: D'Onofrio
authors: Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, I‑71013 Foggia, Italy.
authors: Daniele
authors: D
authors: Sancarlo
authors: Geriatric Unit & Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, I‑71013 Foggia, Italy.
authors: Antonio
authors: A
authors: Greco
authors: Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Department of Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China.
authors: Zhuowei
authors: Z
authors: Yu
mesh_terms: D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000652:urine; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000652:urine; D006801:Humans; D016875:tau Proteins / Q000032:analysis
chemical_list: D015415:Biomarkers; D016875:tau Proteins