Alzheimer discovered the disorder that bears his name in 1906 when he reported the case of a 51-years-old woman (Auguste D.) with presenile dementia with characteristic changes in the cerebral cortex (Alzheimer, 1907, 1911). Alzheimer’s disease (AD), which is the most common cause of dementia, is characterized by slowly progressive decline of cortical functions, particularly cognition and memory. Terry and Davies (1980) pointed out that the presenile form - with onset before age 65 - is identical to the most common form of senile dementia. Thus, the terms AD-type dementia, or probable AD are used for the clinical designation of  both, presenile and senile cases. Confocal image.

The pathological hallmarks of AD consist of a marked cortical atrophy, accumulation of senile plaques (known also as argyrophylic or neuritic plaques), neurofibrillary tangles and neuropil threads in the cerebral cortex. The occurrence of senile plaques was first reported by Blocq and Marinesco (1892) and the characteristic fibrillary changes in neuronal cells were first described and illustrated by Alzheimer (1907). Recently, particularly from the use of a Gallyas silver technique, the accumulation of neuropil threads or curly fibers was recognized as a characteristic cortical lesion in AD (Gallyas, 1971).

Fibrillary amyloid substance accumulates in senile plaques, but also in leptomeningeal and cortical vessel walls (Glenner and Wrong, 1984:, Kang et al., 1987). The major subunit of the amyloid fibrils is a small self-aggregating peptide. This 4-4.3-kDa peptide was designated beta amyloid peptide (Aβ) because of the beta-pleated sheet structure of fibrillary Aβ. Aβ 1-42 has a higher ability to aggregate compared to the shorter Aβ 1-40. This capacity has been related to the two additional C terminal hydrophobic amino acids. Aβ exists in soluble non-toxic monomers, strongly toxic soluble oligomers, called also protofibrils or amyloid derived diffusible ligands (ADDLs), and in the form of less toxic insoluble fibrils. The soluble oligomers of Aβ1-42 are the most toxic. These toxic oligomers form annular or pore-like structures, which morphologically are indistinguishable from a class of pore-forming bacterial toxins (Kirkitadze et al., 2002; Lashuel et al., 2002). Bacteria derived pores or ion-selective channels cause rapid calcium influx through thetargeted cell membranes (Müller et al., 1999). Recent in vitro and in vivo studies showed that Ab is an antimicrobial peptide (AMP) that targets bacterial membranes (Soscia et al., 2010). Aβ oligomers associate with lipid bilayers of bacterial membranes and produce their toxicity through the formation of channels or "pores"causing inappropriate membrane permeabilization and disturbed calcium homeostasis (Lashuel et al., 2002). Abexerts antimicrobial activity against eight common and clinically relevant microorganisms, with a potency equivalent to, and in some cases greater than that of LL-37, another well known AMP (Soscia et al., 2010). AMPs have pro-inflammatory activities and play a role in innate immune responses (Soscia et al., 2010).

Aβ is derived by proteolytic cleavage from a larger, transmembrane amyloid beta precursor protein (APP), which is expressed in a variety of tissues (Kang et al., 1987). APP contains features characteristic of glycosylated cell-surface receptors and revealed to be a proteoglycan core protein (Schubert, 1988). Growing number of evidences suggest that APP plays an important role inthe regulation of immune system responses and in T cell differentiation.

Neurofibrillary tangles contain paired helical filaments (PHFs). The major constituants of these PHFs is the microtubule-associated protein tau. Tau is hyperphosphorylated in PHFs. Such pathological hyperphosphorylation of tau abolishes its ability to bind microtubules and promote microtubule assembly. The pathomechanism of Aβ and tangle formation is still unclear.