ABSTRACT
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At present, the only definitive diagnosis of Alzheimer’s disease (AD), the major cause of late-onset
dementia, is made post mortem, being based on the verification of the pathological hallmarks:
extracellular aggregates of b-amyloid (Ab) peptide (amyloid plaques) and intracellular
neurofibrillary tangles (reviewed in Ref. [1]). By processes not completely understood, the
accumulation of Ab and neurofibrillary tangles produces neurodegeneration, which ultimately
accounts for the clinical signs of the disease. Mild memory impairment at the early stage is followed
by a more global cognitive deficit leading to generalized behavioral impairments and, ultimately,
death. Exactly when the neuropathological changes are manifested clinically is uncertain. There are
several lines of evidence that the neural dysfunction associated with the disease starts several years
before the first clinical phenotypes can be validated or even detected at a time when the
degenerative process has already progressed to an advanced stage with massive cell loss. The
diagnostic value of the levels of the Ab peptide species (a decrease of soluble monomeric species),
increases of specifically phosphorylated tau protein in cerebrospinal fluid (CSF) and the ApoE
genotype are currently being assessed [2,3].
