title: Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects.
abstract: Low cerebrospinal fluid (CSF) Aβ(42) levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ(42) levels than non-carriers. The hypothesis of this investigation was that CSF Aβ(42) levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ(42) levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ(42) levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ(42) levels in controls but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ(42) levels.
authors.affiliation: Northwest Network VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. Electronic address: SteveMillard@comcast.net.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Millard
authors.forename: Franziska
authors.initials: F
authors.lastname: Lutz
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kaye
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Debby
authors.initials: D
authors.lastname: Tsuang
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Bekris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D059748:Proteolysis; D000511:alpha-Macroglobulins / Q000235:genetics*
chemical_list: C578813:A2M protein, human; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; C075222:amyloid beta-protein (1-42)
keywords: A2M; APOE; Alzheimer's disease; Aβ(42); Cerebrospinal fluid; alpha-2-Macroglobulin