title: CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is characterized by progressive impairments in cognitive and behavioral functions with deficits in learning, memory and executive reasoning. Growing evidence points toward brain insulin and insulin-like growth factor (IGF) resistance-mediated metabolic derangements as critical etiologic factors in AD. This suggests that indices of insulin/IGF resistance and their consequences, i.e. oxidative stress, neuro-inflammation, and reduced neuronal plasticity, should be included in biomarker panels for AD. Herein, we examine a range of metabolic, inflammatory, stress, and neuronal plasticity related proteins in early AD, late AD, and aged control postmortem brain, postmortem ventricular fluid (VF), and clinical cerebrospinal fluid (CSF) samples. In AD brain, VF, and CSF samples the trends with respect to alterations in metabolic, neurotrophin, and stress indices were similar, but for pro-inflammatory cytokines, the patterns were discordant. With the greater severities of dementia and neurodegeneration, the differences from control were more pronounced for late AD (VF and brain) than early or moderate AD (brain, VF and CSF). The findings suggest that the inclusion of metabolic, neurotrophin, stress biomarkers in AβPP-Aβ+pTau CSF-based panels could provide more information about the status and progression of neurodegeneration, as well as aid in predicting progression from early- to late-stage AD. Furthermore, standardized multi-targeted molecular assays of neurodegeneration could help streamline postmortem diagnoses, including assessments of AD severity and pathology.
authors.affiliation: Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School, Providence, RI, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School, Providence, RI, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tong
authors.affiliation: Department of Medicine, Warren Alpert Medical School, Providence, RI, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hang
authors.affiliation: Departments of Medicine, Rhode Island Hospital, Brown University, Providence, RI, USA.
authors.forename: Chetram
authors.initials: C
authors.lastname: Deochand
authors.affiliation: Department of Medicine, Pathology (Neuropathology), Neurology and Neurosurgery, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: de la Monte
keywords: Amyloid; Biomarkers; Cerebrospinal fluid; Glucose metabolism; Insulin resistance; Luminex; Neurodegeneration; Neurotrophins; Tau