Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

• Published in: Neurobiology of aging Vol. 30; no. 5; pp. 682 - 690
• Main Authors: Brys, Miroslaw, Pirraglia, Elizabeth, Rich, Kenneth, Rolstad, Sindre, Mosconi, Lisa, Switalski, Remigiusz, Glodzik-Sobanska, Lidia, De Santi, Susan, Zinkowski, Ray, Mehta, Pankaj, Pratico, Domenico, Saint Louis, Leslie A., Wallin, Anders, Blennow, Kaj, de Leon, Mony J.
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.05.2009; Elsevier
• Subjects: 80 and over; Aged; Aged, 80 and over; Alzheimer Disease; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Protein; analysis; Biological and medical sciences; Biological Markers; Biomarkers - analysis; Biomarkers - cerebrospinal fluid; cerebrospinal fluid; Cognition Disorders; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - diagnosis; Cohort Studies; CSF biomarkers; Development. Senescence. Regeneration. Transplantation; diagnosis; Disease Progression; Early detection; Early Diagnosis; Female; Fundamental and applied biological sciences. Psychology; Geriatrics; Humans; Internal Medicine; Isoprostanes; Isoprostanes - analysis; Isoprostanes - cerebrospinal fluid; Longitudinal; Longitudinal Studies; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Mild cognitive impairment; Neurology; Peptide Fragments; Peptide Fragments - analysis; Peptide Fragments - cerebrospinal fluid; Prediction; Predictive Value of Tests; Prognosis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; tau Proteins; tau Proteins - analysis; tau Proteins - cerebrospinal fluid; Vertebrates: nervous system and sense organs; Longitudinal; CSF biomarkers; Mild cognitive impairment; Alzheimer's disease; Early detection; Prediction; Nervous system diseases; Senescence; Alzheimer disease; Biological marker; Cerebrospinal fluid; Cerebral disorder; Central nervous system disease; Early; Degenerative disease; mild cognitive impairment
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.08.010

To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD). A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau 231), amyloid beta (Aβ) Aβ 42/Aβ 40 ratio, isoprostane (IP) as well as P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios. At baseline and at follow-up MCI-AD showed higher levels P-tau 231, T-tau, IP, P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios and lower Aβ 42/Aβ 40 than MCI-MCI or NL-NL. Baseline P-tau 231 best predicted MCI-AD (80%, p < 0.001) followed in accuracy by P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios (both 75%, p's < 0.001), T-tau (74%, p < 0.001), Aβ 42/Aβ 40 (69%, p < 0.01), and IP (68%, p < 0.01). Only IP showed longitudinal effects ( p < 0.05). P-tau 231 is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.