Three Alzheimer disease (AD) causing genes : amyloid precursor protein , presenilin 1 , and presenilin 2 ; and one susceptibility gene , apolipoprotein E , have been identified . Jointly these genes account for approximately 50% of the total genetic effect on AD risk , leaving 50% of the genetic effect unexplained . Studies indicate that one of the most promising locations for a fifth AD gene is the centromeric region of chromosome 12 . This chromosomal region contains several genes that are potential candidates for the chromosome 12 AD gene . The Pedigree Disequilibrium Test (PDT) was used to test for allelic association and linkage between AD and nine chromosome 12 candidate genes in a series of multiplex ( 2 AD individuals/family) AD families as diagnosed by NINCDS-ADRDA criteria . The genes examined were the neurotrophin-3 (NTF3) ; tumor necrosis factor receptor 1 (TNFR1) ; human complement component (C1R) ; oxidized low-density lipoprotein receptor (OLR1 ) ; islet amyloid polypeptide (IAPP) ; Kirsten rat sarcom 2 viral oncogene (KRAS2) ; mitochondrial ATP synthase , ; subunit (ATP5B) ; human brain sodium channel 2 (hBNaC2) ; and interleukin-4 Stat (IL-4 Stat) . These genes are located in an approximately 65 cM region spanning 12p13 to 12q13 . PDT p-values were not statistically significant for any of the candidate genes tested , ranging from 0 .23 (IAPP) to 0 .94 (KRAS2) . These data provide no evidence that any of the candidate genes examined here is the sought after chromosome 12 AD susceptibility gene .
|Original language||English (US)|
|Number of pages||6|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Clinical Neurology