OBJECTIVE: To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD. RESULTS: Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD. CONCLUSIONS: Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42.
OBJECTIVE: To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD. RESULTS: Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD. CONCLUSIONS: Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42.
Authors: A Siderowf; S X Xie; H Hurtig; D Weintraub; J Duda; A Chen-Plotkin; L M Shaw; V Van Deerlin; J Q Trojanowski; C Clark Journal: Neurology Date: 2010-08-18 Impact factor: 9.910
Authors: Craig Ritchie; Nadja Smailagic; Anna H Noel-Storr; Obioha Ukoumunne; Emma C Ladds; Steven Martin Journal: Cochrane Database Syst Rev Date: 2017-03-22
Authors: Clifford R Jack; Heather J Wiste; Prashanthi Vemuri; Stephen D Weigand; Matthew L Senjem; Guang Zeng; Matt A Bernstein; Jeffrey L Gunter; Vernon S Pankratz; Paul S Aisen; Michael W Weiner; Ronald C Petersen; Leslie M Shaw; John Q Trojanowski; David S Knopman Journal: Brain Date: 2010-10-08 Impact factor: 13.501
Authors: Maartje I Kester; Charlotte E Teunissen; Courtney Sutphen; Elizabeth M Herries; Jack H Ladenson; Chengjie Xiong; Philip Scheltens; Wiesje M van der Flier; John C Morris; David M Holtzman; Anne M Fagan Journal: Alzheimers Res Ther Date: 2015-09-17 Impact factor: 6.982
Authors: Craig Ritchie; Nadja Smailagic; Anna H Noel-Storr; Yemisi Takwoingi; Leon Flicker; Sam E Mason; Rupert McShane Journal: Cochrane Database Syst Rev Date: 2014-06-10