Association of cerebrospinal fluid A beta(42) with A2M gene in cognitively normal subjects

作者：Millard Steven P^*; Lutz Franziska; Li Ge; Galasko Douglas R; Farlowg Martin R; Quinn Joseph F; Kaye Jeffrey A; Leverenz James B; Tsuang Debby; Yu Chang En; Peskind Elaine R; Bekris Lynn M

来源：Neurobiology of Aging, 2014, 35(2): 357-364.

DOI：10.1016/j.neurobiolaging.2013.07.027

• Alzheimer's disease
• Cerebrospinal fluid
• A beta(42)
• alpha-2-Macroglobulin
• A2M
• APOE

Low cerebrospinal fluid (CSF) A beta(42) levels correlate with increased brain Ab deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Ab from the brain. In addition, APOE epsilon 4 carriers have lower CSF A beta(42) levels than non-carriers. The hypothesis of this investigation was that CSF A beta(42) levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Ab from the brain. CSF A beta(42) levels were tested for associations with Ab degradation and clearance genes and APOE epsilon 4. 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 A beta(42) levels were associated with APOE epsilon 4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF A beta(42) levels in controls but not in AD patients, even after adjusting for APOE epsilon 4. These results suggest that genetic variation within the A2M gene influences CSF A beta(42) levels.

• 出版日期2014-2