Question

What are the two main neuropathological hallmarks of Alzheimer's disease? Compare and contrast their anatomical location and protein composition.

Short answer

Answer: The two main neuropathological hallmarks of Alzheimer's disease are amyloid-beta plaques and neurofibrillary tangles. Amyloid-beta plaques are extracellular deposits in the gray matter, primarily found in the neocortex and hippocampus regions, and are composed of aggregated amyloid-beta peptides. Neurofibrillary tangles are intracellular structures within neurons, mainly located in the hippocampus, entorhinal cortex, and basal forebrain regions, and are composed of hyperphosphorylated tau protein.

Step-by-step solution

Identify the two main neuropathological hallmarks of Alzheimer's disease

The two main neuropathological hallmarks of Alzheimer's disease are amyloid-beta plaques and neurofibrillary tangles.

Explain the anatomical location of amyloid-beta plaques

Amyloid-beta plaques tend to form primarily in the extracellular spaces of the brain's gray matter, particularly in the neocortex and hippocampus regions. These regions are responsible for memory and cognitive functions, which are significantly affected in Alzheimer's disease.

Explain the protein composition of amyloid-beta plaques

Amyloid-beta plaques are formed by the accumulation and aggregation of amyloid-beta (Aβ) peptides. These peptides are produced when the amyloid precursor protein (APP), a transmembrane protein, is cleaved sequentially by beta-secretase and gamma-secretase enzymes. The amyloid-beta peptides then aggregate into insoluble fibrils and form the characteristic plaques observed in Alzheimer's disease.

Explain the anatomical location of neurofibrillary tangles

Neurofibrillary tangles are mainly found inside the neurons of the brain, particularly in the hippocampus, entorhinal cortex, and basal forebrain regions. These are associated with memory and cognitive functions, which deteriorate in Alzheimer's disease.

Explain the protein composition of neurofibrillary tangles

Neurofibrillary tangles are composed of hyperphosphorylated tau protein. In a healthy brain, tau protein binds to and stabilizes microtubules, which are essential for maintaining the structure and function of neurons. In Alzheimer's disease, abnormal phosphorylation of tau protein reduces its affinity for microtubules, leading to the formation of insoluble twisted filaments called paired helical filaments (PHFs). These PHFs aggregate to form the neurofibrillary tangles observed in Alzheimer's patients.

Compare and contrast the hallmarks in terms of anatomical location and protein composition

While both amyloid-beta plaques and neurofibrillary tangles are primarily found in regions related to memory and cognitive functions, they differ in their specific locations within the brain. Amyloid-beta plaques are extracellular deposits in the gray matter, while neurofibrillary tangles are located intracellularly within neurons. In terms of protein composition, amyloid-beta plaques consist of aggregated amyloid-beta peptides, which are cleaved from APP. On the other hand, neurofibrillary tangles are composed of hyperphosphorylated tau protein, which normally stabilizes microtubules but becomes dysfunctional due to its abnormal phosphorylation.