BACKGROUND: Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease. OBJECTIVE: To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT). DESIGN: Retrospective analysis of CSF biomarkers and clinical data. SETTING: An academic Alzheimer disease research center. PARTICIPANTS: Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years). MAIN OUTCOME MEASURES: Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance. RESULTS: The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values. CONCLUSIONS: In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.
BACKGROUND: Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease. OBJECTIVE: To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT). DESIGN: Retrospective analysis of CSF biomarkers and clinical data. SETTING: An academic Alzheimer disease research center. PARTICIPANTS: Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years). MAIN OUTCOME MEASURES: Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance. RESULTS: The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values. CONCLUSIONS: In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.
Authors: Trey Sunderland; Gary Linker; Nadeem Mirza; Karen T Putnam; David L Friedman; Lida H Kimmel; Judy Bergeson; Guy J Manetti; Matthew Zimmermann; Brian Tang; John J Bartko; Robert M Cohen Journal: JAMA Date: 2003 Apr 23-30 Impact factor: 56.272
Authors: B Winblad; K Palmer; M Kivipelto; V Jelic; L Fratiglioni; L-O Wahlund; A Nordberg; L Bäckman; M Albert; O Almkvist; H Arai; H Basun; K Blennow; M de Leon; C DeCarli; T Erkinjuntti; E Giacobini; C Graff; J Hardy; C Jack; A Jorm; K Ritchie; C van Duijn; P Visser; R C Petersen Journal: J Intern Med Date: 2004-09 Impact factor: 8.989
Authors: William E Klunk; Henry Engler; Agneta Nordberg; Yanming Wang; Gunnar Blomqvist; Daniel P Holt; Mats Bergström; Irina Savitcheva; Guo-feng Huang; Sergio Estrada; Birgitta Ausén; Manik L Debnath; Julien Barletta; Julie C Price; Johan Sandell; Brian J Lopresti; Anders Wall; Pernilla Koivisto; Gunnar Antoni; Chester A Mathis; Bengt Långström Journal: Ann Neurol Date: 2004-03 Impact factor: 10.422
Authors: H Hampel; S J Teipel; T Fuchsberger; N Andreasen; J Wiltfang; M Otto; Y Shen; R Dodel; Y Du; M Farlow; H-J Möller; K Blennow; K Buerger Journal: Mol Psychiatry Date: 2004-07 Impact factor: 15.992
Authors: M Kanai; E Matsubara; K Isoe; K Urakami; K Nakashima; H Arai; H Sasaki; K Abe; T Iwatsubo; T Kosaka; M Watanabe; Y Tomidokoro; M Shizuka; K Mizushima; T Nakamura; Y Igeta; Y Ikeda; M Amari; T Kawarabayashi; K Ishiguro; Y Harigaya; K Wakabayashi; K Okamoto; S Hirai; M Shoji Journal: Ann Neurol Date: 1998-07 Impact factor: 10.422
Authors: John R Cirrito; Patrick C May; Mark A O'Dell; Jennie W Taylor; Maia Parsadanian; Jeffrey W Cramer; James E Audia; Jeffrey S Nissen; Kelly R Bales; Steven M Paul; Ronald B DeMattos; David M Holtzman Journal: J Neurosci Date: 2003-10-01 Impact factor: 6.167
Authors: B DaRocha-Souto; M Coma; B G Pérez-Nievas; T C Scotton; M Siao; P Sánchez-Ferrer; T Hashimoto; Z Fan; E Hudry; I Barroeta; L Serenó; M Rodríguez; M B Sánchez; B T Hyman; T Gómez-Isla Journal: Neurobiol Dis Date: 2011-09-13 Impact factor: 5.996
Authors: Rebecca Craig-Schapiro; Richard J Perrin; Catherine M Roe; Chengjie Xiong; Deborah Carter; Nigel J Cairns; Mark A Mintun; Elaine R Peskind; Ge Li; Douglas R Galasko; Christopher M Clark; Joseph F Quinn; Gina D'Angelo; James P Malone; R Reid Townsend; John C Morris; Anne M Fagan; David M Holtzman Journal: Biol Psychiatry Date: 2010-11-15 Impact factor: 13.382
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Michal Figurski; Els Coart; Kaj Blennow; Holly Soares; Adam J Simon; Piotr Lewczuk; Robert A Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Acta Neuropathol Date: 2011-02-11 Impact factor: 17.088