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Pathology-Alzheimer's Disease
I. Definition & Epidemiology:
I. Definition & Epidemiology:
- Definition: Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by dementia and histopathologically by neuronal loss in the cerebral cortex, accompanied by amyloid plaques and neurofibrillary tangles. Crucially, it's the most common cause of dementia.
- Epidemiology:
- Incidence dramatically increases with age (5% >65 years old, 20% >80 years old).
- Represents a significant socioeconomic burden on healthcare systems.
- Aetiology (Cause): The cause is unknown in most cases. A small percentage are familial, linked to genetic mutations in the amyloid precursor protein (APP) gene on chromosome 21.
- Pathogenesis (Mechanism):
- AD is considered a "proteinopathy," focusing on the abnormal accumulation of amyloid-beta (Aβ) and tau proteins.
- Aβ peptides are derived from APP through secretase enzymes.
- The exact mechanism by which Aβ and tau accumulation leads to neuronal loss remains unclear—this is a key area of ongoing research.
- Early Stages: Begins with memory loss, especially recent memory and new learning difficulties. Progressive decline in daily activities (finances, shopping).
- Middle Stages: Loss of motor skills impacts dressing, cooking, and cleaning.
- Late Stages: Agitation, restlessness, wandering, and disinhibition emerge, causing distress for family and caregivers. Eventually, speech loss, immobility, and incontinence occur.
- Macroscopy (Gross Anatomy):
- Reduced brain weight (often <1000g).< />pan>
- Cortical atrophy, particularly in the temporal lobe and hippocampus.
- Histopathology (Microscopic Anatomy):
- Key Features: Abundant neuritic plaques and neurofibrillary tangles in the cerebral cortex, alongside neuronal and synaptic loss.
- Neuritic Plaques: Spherical collections of distorted neuronal processes around a central amyloid core, primarily composed of Aβ protein.
- Neurofibrillary Tangles: Intracellular accumulations of paired helical filaments within neurons; mainly composed of tau protein.
- Death typically occurs approximately 10 years post-diagnosis, often due to complications like pneumonia.
- Amyloid-beta (Aβ) plaques: Extracellular deposits, key hallmark of AD.
- Neurofibrillary tangles: Intracellular accumulations of tau protein, another hallmark of AD.
- APP (Amyloid Precursor Protein): A protein implicated in familial forms of AD.
- Tau protein: A microtubule-associated protein whose abnormal accumulation contributes to neurofibrillary tangles.
- Proteinopathy: A disease caused by misfolded or aggregated proteins.
- The relationship between Aβ and tau accumulation and neuronal death needs further study.
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