Most cases of the disease are sporadic, they have a late onset (in patients over 60 years) and an unknown etiology. However, from 5 to 15% cases have a familial character, a half of these cases has an earlier onset (in age less than 60 years), and is usually associated with specific genetic mutations.
Typical morphological changes are the extracellular accumulation of the α-amyloid and the intracellular neurofibrillar glomes (paired helical filaments), the development of the senile plaques and the loss of neurons. There are usually a cortical atrophy, reduced glucose consumption, as well as a decrease in cerebral perfusion in the parietal lobe, temporal cortex and prefrontal cortex.
At least five specific genetic loci, located on the 1st, 12th, 14th, 19th and 21th chromosomes, influence on the onset and progression of Alzheimer's disease. In the development of the disease genes, encoding processing of the precursor protein presenilin I and presenilin II, are is involved. Mutations in these genes can alter processing of α-amyloid precursor protein, leading to the accumulation of fibrillar aggregates of the α-amyloid. α-amyloid can facilitate death of neurons and formation of the neurofibrillar glomes and senile plaques which consist of degenerative changes of axons and dendrites, astrocytes and glial cells, located around the amyloid nucleus.
Other genetic determinants include alleles of apolipoprotein E (apo E). Apolipoprotein E influences on the accumulation of α-amyloid, cytoskeleton integrity and the effectiveness of neuron recovery. Risk of Alzheimer's disease is greatly increased in people, having four alleles, and is reduced in those ones, who have two alleles.
Other common abnormalities include an increase of concentration in cerebrospinal fluid and brain of protein taurine (components of neurofibrillar glomes and α-amyloid) and a decrease of choline acetyltransferase and various neurotransmitters (in particular, somatostatin).
The relationship of the environmental factors (exogenous) (including low levels of hormones, exposure to the effects of metals) and Alzheimer's disease is still under study, but no correlation has been confirmed yet.