Familial AD

Protein-protein interactions between heterodimeric protein pairs that form only transient interactions can be detected, y-secre-tase is presenilin-1 (PS1) dependent [51-53]. PS1 is a 467-amino acid, 9-transmembrane domain protein. Over 100 documented single point mutations are known to cause autosomal-dominant familial AD (FAD) [54], in which the ratio of the more fibrilogenic variety of A ft (A/142) to the less fibrilogenic variety (A/140) is increased. Chinese hamster ovary (CHO) cells were stably transfected with human APP and either wild type or mutant PS1 [4, 55]. 

PS-2, are found as the most frequent causes of early onset familial AD cases [5]. The prese-nilins are involved in APP processing by enzymes called secretases [6]. 

In addition to age, other factor s are associated with an inareased risk of AD. In developed countries, AD appears to be more common in v omen. Lack of education is a risk factor for senile dementia in China and Europe (Zhang et al., 1990 Schmand et al., 1997). Head daunra is also a risk factor for both sporadic (Mortimer et al., 1991) and familial AD (Guo et al., 2000). Silent myocardial infarcts and coronary stenosis triple the risk for AD (Aronson etal., 1990 Sparks etal., 1990), suggesting the importance of vascular risk factors. Other potential risk factors being studied include diabetes and hypertension (Ott et al., 1999 Peila et al., 2002 Qiu etal., 2005). As discussed below, a large number of genetic mutations are now associated with either early-onset AD or with increased risk of late-onset AD. 

While variants in these three genes (APP, PSl, and PS2) account for between 30% and 50% of early-onset familial AD, overall they account for less than 2% of all cases of AD (Klaver et al., 1998 Finckh et al., 2000 Liddell et al., 1995 Rosenberg et al., 2000). 

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