Alzheimer’s disease (AD), the cause of one of the most common types of dementia, is pathologically characterized by cholinergic deficits, extracellular amyloid deposit, intraneuronal neurofibrillary tangles, gliosis, and neuronal and synaptic
loss.
The
primary clinical manifestation of AD is a profound global dementia that is marked by severe amnesia with additional deficits in language, executive functions, attention, and visuospatial and constructional abilities. Molecular genetic studies
have
identified at least three genes that, when mutated, cause the autosomal dominant, early-onset familial form of the disease The late-onset, most common forms of the disease are likely to be associated with various genetic susceptibility factors.
Research
on the underlying pathophysiological dysfunction finally disclosed more disease-specific processes. Of particular importance is the identification and characterization of the secretases involved in endoproteolytic processing of β-amyloid
precursor
protein, the precursor of the amyloid β-peptide(Aβ). It is generally accepted that Aβ plays a pivotal role in the pathogenesis of AD, and that reducing brain Aβ levels may be a disease-modifying strategy. By inhibiting one or both
amyloidogenic
secretases and immunization with Aβ, neuropathological features of AD can be prevented or alleviated.
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