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

Age at maturity in cavies and guinea-pigs (Cavia aperea and Cavia aperea f. porcellus): influence of social factors

Trillmich F, Laurien-Kehnen C, Adrian A, Linke S. Age at maturity in cavies and guinea-pigs (Cavia aperea and Cavia aperea f. porcellus): influence of social factors. JOURNAL OF ZOOLOGY. 2006;268(3):285-294.Age at maturity, a particularly important parameter in the life history of small mammals, contributes greatly to fitness. Social influences on age at maturity have been demonstrated for altricial rodents, in particular, mice. Nothing is known about such effects in precocial small mammals. Wild cavies Cavia aperea are born in a highly precocial state and mature early in life, briefly after weaning. We investigated whether the wild cavy C. aperea and the domestic guinea-pig Cavia aperea f. porcellus reach maturity earlier in the presence of adults of the opposite sex. Juvenile females kept in pairs without males showed first vaginal opening (=oestrus) when 59 days old in cavies and at about 40 days in the guinea-pig. However, in the company of adult males, cavy females kept in pairs reached maturity when about 30 days old, and guinea-pig females when 26 days old. Most cavy females experienced successful pregnancy following first vaginal opening. In cavies, female mass at birth and at first oestrus was not correlated with age at first oestrus. In guinea-pigs, birth mass predicted age at maturity only when a male was present. The growth rate from birth to first oestrus related to age at first oestrus. In the wild cavy, the presence of a male appeared to influence maturation more between days 25 and 30 than earlier in life. Male C. aperea matured and had fully descended testes when about 65-70 days old. All male cavies produced abundant motile sperm from day 75. First successful copulations occurred at about the same age. Surprisingly, the priming effect of the presence of an adult male on female maturation proved stronger in these highly precocial caviomorphs than in altricial rodents investigated so far