Autophagy is a major intracellular degeneration pathway involved in the elimination and recycling of damaged organelles and long-lived
proteins by lysosomes. Many of the pathological factors, which trigger
neurodegenerative diseases, can perturb the autophagy activity, which is associated with misfolded
protein aggregates accumulation in these disorders.
Alzheimer's disease, the first
neurodegenerative disorder between
dementias, is characterized by two aggregating
proteins, β-
amyloid peptide (plaques) and τ-
protein (tangles). In
Alzheimer's disease autophagosomes dynamically form along neurites within neuronal cells and in synapses but effective clearance of these structures needs retrograde transportation towards the neuronal
soma where there is a major concentration of lysosomes. Maturation of autophago-lysosomes and their retrograde trafficking are perturbed in
Alzheimer's disease, which causes a massive concentration of autophagy elements along degenerating neurites. Transportation system is disturbed along defected microtubules in
Alzheimer's disease brains. τ-
protein has been found to control the stability of microtubules, however, phosphorylation of τ-
protein or an increase in the total level of τ-
protein can cause dysfunction of neuronal cells microtubules. Current evidence has shown that autophagy is developing in
Alzheimer's disease brains because of ineffective degradation of autophagosomes, which hold
amyloid precursor
protein-rich organelles and
secretases important for β-
amyloid peptides generation from
amyloid precursor. The combination of raised autophagy induction and abnormal clearance of β-
amyloid peptide-generating autophagic vacuoles creates circumstances helpful for β-
amyloid peptide aggregation and accumulation in
Alzheimer's disease. However, the key role of autophagy in
Alzheimer's disease development is still under consideration today. One point of view suggests that abnormal autophagy induction causes a concentration of autophagic vacuoles rich in
amyloid precursor
protein, β-
amyloid peptide and the elements crucial for its formation, whereas other hypothesis points to marred autophagic clearance or even decrease in autophagic effectiveness playing a role in maturation of
Alzheimer's disease. In this review we present the recent evidence linking autophagy to
Alzheimer's disease and the role of autophagic regulation in the development of full-blown
Alzheimer's disease.