New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

BREAST-MILK MONITORING TO MEASURE MICHIGAN'S CONTAMINATION WITH POLYBROMINATED BIPHENYLS

In 1973 and 1974, several thousand Michigan dairy farms were contaminated by polybrominated biphenyls (P.B.B.) as the result of an industrial accident. An unknown quantity of contaminated meat and dairy products entered the food chain before contaminated farms were quarantined. To determine the extent of human exposure, P.B.B. concentrations were measured in human breast milk, which was collected in a random-sample survey from nursing mothers throughout Michigan. 96% of 53 samples from Michigan's lower peninsula and 43% of 42 samples from the less densely populated upper peninsula contained detectable levels of P.B.B. These data indicate that about 8 million of Michigan's 9[middle dot]1 million residents have detectable body burdens of P.B.B.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22528/1/0000072.pd

Historical changes in serum PCB and DDT levels in an environmentally-exposed cohort

A previously characterized cohort of 115 Great Lakes fisheaters and 95 non-fisheating controls was re-examined in 1989 to evaluate changes that had occurred in serum PCB and DDT levels since the 1982 study. Substantial and significant decreases in mean serum DDT levels had occurred in both fisheaters (25.8 ppb vs 15.6 ppb) and controls (9.6 ppb vs 6.8 ppb) ppb=ng/gPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48077/1/244_2004_Article_BF00212554.pd