2009 | Charles Duyckaerts · Benoît Delatour · Marie-Claude Potier
The chapter discusses the classification and basic pathology of Alzheimer's disease (AD), focusing on the accumulation of proteins, neuronal and synaptic losses, and reactive processes. Extracellular accumulation of amyloid beta (Aβ) peptides occurs in the brain parenchyma as diffuse, focal, or stellate deposits, often involving vessel walls. Tau protein accumulation, a key histopathological correlate of clinical symptoms, manifests as neurofibrillary tangles and senile plaques. The progression of tau pathology is stereotyped from the entorhinal cortex to the hippocampus and isocortex. Neuronal loss is heterogeneous and area-specific, while synaptic loss is linked to Aβ oligomers. Various clinico-pathological types of AD are described based on lesion type, onset, cause, and associated lesions. The production and clearance of Aβ are balanced, with mutations in APP, presenilins, and other genes affecting this balance. Aβ oligomers are toxic and can act through glutamate receptors, influencing synaptic function. Aβ can be degraded by multiple enzymes and cleared from the brain parenchyma through various pathways. Different types of Aβ deposits are identified using anti-Aβ antibodies, and their association with proteins, lipids, and cells is discussed.The chapter discusses the classification and basic pathology of Alzheimer's disease (AD), focusing on the accumulation of proteins, neuronal and synaptic losses, and reactive processes. Extracellular accumulation of amyloid beta (Aβ) peptides occurs in the brain parenchyma as diffuse, focal, or stellate deposits, often involving vessel walls. Tau protein accumulation, a key histopathological correlate of clinical symptoms, manifests as neurofibrillary tangles and senile plaques. The progression of tau pathology is stereotyped from the entorhinal cortex to the hippocampus and isocortex. Neuronal loss is heterogeneous and area-specific, while synaptic loss is linked to Aβ oligomers. Various clinico-pathological types of AD are described based on lesion type, onset, cause, and associated lesions. The production and clearance of Aβ are balanced, with mutations in APP, presenilins, and other genes affecting this balance. Aβ oligomers are toxic and can act through glutamate receptors, influencing synaptic function. Aβ can be degraded by multiple enzymes and cleared from the brain parenchyma through various pathways. Different types of Aβ deposits are identified using anti-Aβ antibodies, and their association with proteins, lipids, and cells is discussed.