title: Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer's disease.
abstract: The frequent co-occurrence of Alzheimer's disease (AD) pathology in patients with normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of faulty cerebrospinal fluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of amyloid-beta peptide (Abeta) in CSF in preclinical and early AD. CSF biomarker data (Abeta, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volumes were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 288 subjects classified as being either normal (n=87), having the syndrome of mild cognitive impairment (n=136), or mild AD (n=65). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. For controls, ventricular volume was negatively associated with CSF Abeta in APOE epsilon4 positive subjects. A different pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not Abeta in epsilon4 positive subjects. Increased ventricular volume may be associated with decreased levels of CSF Abeta in preclinical AD. The basis for the apparent effect of APOE epsilon4 genotype on the relationship of ventricular volume to Abeta and tau levels is unknown, but could involve altered CSF-blood-brain barrier function during the course of disease.
authors.affiliation: Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. BOtt@lifespan.org
authors.forename: Brian R
authors.initials: BR
authors.lastname: Ott
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Assawin
authors.initials: A
authors.lastname: Gongvatana
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
authors.forename: Conrad E
authors.initials: CE
authors.lastname: Johanson
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
authors.forename: John E
authors.initials: JE
authors.lastname: Donahue
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Silverberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000209:etiology / Q000473:pathology; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D016875:tau Proteins