ABSTRACT
There has been a major expansion in recent years on research into the genetic
causes of dementia, and a simple search on the PubMed database including the
terms “Dementia” and “Genetics” in March 2005 identified more than 13,000
references from 1964. Following the description of Alzheimer’s first case, the
first suggestion that genetic factors may play a role in Alzheimer’s disease (AD)
were reported in a paper of Lua (1920) and subsequently in a case report by
Flugel (1922), both speculating a possible genetic inheritance of the disease.
Since then, from 1930 to 1990, more than 50 pedigrees with a familial form of
AD have been described, suggesting that familial aggregation is a common
feature of AD. This observation has been successively confirmed by several
epidemiological studies (1,2). The analysis of these collected families and the
possible genotype-phenotype correlations, together with the outstanding progress
of molecular biological techniques, have made the field of dementia genetics in
the past 15 years an area of intense research and fruitful discoveries. This
information assembled in the past few years has led to the principal finding that
analysis of the genetic mechanisms underlying familial clustering of the disease
is likely to be directly relevant to the pathogenesis of the common and apparently
sporadic forms of AD. In addition, today’s knowledge of genetic factors is
currently evolving and leading to the progressive definition of a putative cascade
of biochemical events that, applied to early diagnosis, therapeutic trials,
treatment, and preventive approaches, could provide fundamental advances to
prevent and cure AD and other dementias.
