OBJECTIVE: Plasma A beta levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD). METHODS: We measured plasma A beta in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early-onset AD genes and determined their ApoE genotypes. RESULTS: Plasma A beta is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE epsilon 4 or pathogenic coding mutations in the known early-onset AD genes. CONCLUSIONS: The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late-onset Alzheimer disease by increasing A beta.
OBJECTIVE: Plasma A beta levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD). METHODS: We measured plasma A beta in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early-onset AD genes and determined their ApoE genotypes. RESULTS: Plasma A beta is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE epsilon 4 or pathogenic coding mutations in the known early-onset AD genes. CONCLUSIONS: The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late-onset Alzheimer disease by increasing A beta.
Authors: Joseph L Price; Daniel W McKeel; Virginia D Buckles; Catherine M Roe; Chengjie Xiong; Michael Grundman; Lawrence A Hansen; Ronald C Petersen; Joseph E Parisi; Dennis W Dickson; Charles D Smith; Daron G Davis; Frederick A Schmitt; William R Markesbery; Jeffrey Kaye; Roger Kurlan; Christine Hulette; Brenda F Kurland; Roger Higdon; Walter Kukull; John C Morris Journal: Neurobiol Aging Date: 2009-04-18 Impact factor: 4.673
Authors: K Blennow; G De Meyer; O Hansson; L Minthon; A Wallin; H Zetterberg; P Lewczuk; H Vanderstichele; E Vanmechelen; J Kornhuber; J Wiltfang; I Heuser; W Maier; C Luckhaus; E Rüther; M Hüll; H Jahn; H J Gertz; L Frölich; H Hampel; R Pernetzki Journal: J Nutr Health Aging Date: 2009-03 Impact factor: 4.075
Authors: Muthu Ramakrishnan; Karunya K Kandimalla; Thomas M Wengenack; Kyle G Howell; Joseph F Poduslo Journal: Biochemistry Date: 2009-11-03 Impact factor: 3.162
Authors: T T Seppälä; S-K Herukka; T Hänninen; S Tervo; M Hallikainen; H Soininen; T Pirttilä Journal: J Neurol Neurosurg Psychiatry Date: 2010-05-16 Impact factor: 10.154