Classification and basic pathology of Alzheimer disease

• Published in: Acta neuropathologica Vol. 118; no. 1; pp. 5 - 36
• Main Authors: Duyckaerts, Charles, Delatour, Benoît, Potier, Marie-Claude
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2009; Springer Nature B.V
• Subjects: Age of Onset; Alzheimer Disease - classification; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Brain - blood supply; Brain - metabolism; Brain - pathology; Cell Death; Disease Progression; DNA-Binding Proteins - metabolism; Gliosis - complications; Humans; Lewy Bodies - pathology; Medicine; Medicine & Public Health; Nerve Degeneration - pathology; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurogenesis; Neuronal Plasticity; Neurons - pathology; Neurons - physiology; Neurosciences; Pathology; Peptides; Plaque, Amyloid - pathology; Proteins; Review; Sclerosis; Synaptic Transmission; tau Proteins - metabolism; Tauopathies - pathology; Tauopathies - physiopathology; Entorhinal Cortex; Cerebral Amyloid Angiopathy; Senile Plaque; Alzheimer Disease; Neuritic Plaque
• ISSN: 0001-6322; 1432-0533; 1432-0533
• DOI: 10.1007/s00401-009-0532-1

The lesions of Alzheimer disease include accumulation of proteins, losses of neurons and synapses, and alterations related to reactive processes. Extracellular Aβ accumulation occurs in the parenchyma as diffuse, focal or stellate deposits. It may involve the vessel walls of arteries, veins and capillaries. The cases in which the capillary vessel walls are affected have a higher probability of having one or two apoε 4 alleles. Parenchymal as well as vascular Aβ deposition follows a stepwise progression. Tau accumulation, probably the best histopathological correlate of the clinical symptoms, takes three aspects: in the cell body of the neuron as neurofibrillary tangle, in the dendrites as neuropil threads, and in the axons forming the senile plaque neuritic corona. The progression of tau pathology is stepwise and stereotyped from the entorhinal cortex, through the hippocampus, to the isocortex. The neuronal loss is heterogeneous and area-specific. Its mechanism is still discussed. The timing of the synaptic loss, probably linked to Aβ peptide itself, maybe as oligomers, is also controversial. Various clinico-pathological types of Alzheimer disease have been described, according to the type of the lesions (plaque only and tangle predominant), the type of onset (focal onset), the cause (genetic or sporadic) and the associated lesions (Lewy bodies, vascular lesions, hippocampal sclerosis, TDP-43 inclusions and argyrophilic grain disease).