Histology · Year 1 · from Histology
Case 1: Alzheimer Disease
Clinical Image
Source: Wikipedia - Neurofibrillary Tangle - CC BY-SA 3.0
Case Presentation
A 72-year-old retired professor is brought by his wife who reports progressive memory problems over 3 years. He forgets recent conversations, repeats questions, and recently got lost driving to a familiar location. He has also become withdrawn and apathetic. Neurological examination reveals impaired short-term memory with inability to recall 3 words after 5 minutes, difficulty with serial 7s and clock drawing, but intact motor and sensory function. MRI brain shows hippocampal atrophy and enlarged lateral ventricles. CSF analysis reveals decreased amyloid-beta-42 and elevated phosphorylated tau protein. He is diagnosed with probable Alzheimer disease. The neuropathological hallmarks (demonstrated in autopsy studies) are senile plaques (extracellular deposits of amyloid-beta peptide) and neurofibrillary tangles (intracellular aggregates of hyperphosphorylated tau protein). Neurofibrillary tangles appear as flame-shaped intraneuronal inclusions composed of paired helical filaments of abnormally phosphorylated tau. The tau protein normally stabilizes microtubules; when hyperphosphorylated, it detaches and aggregates, disrupting axonal transport. He is started on cholinesterase inhibitors for symptomatic treatment.
Key Learning Points
- Tau protein normally stabilizes microtubules essential for axonal transport
- In Alzheimer disease, tau becomes hyperphosphorylated, detaches from microtubules, and aggregates into neurofibrillary tangles
- Disruption of axonal transport (which requires intact microtubules) leads to synaptic dysfunction and neuronal death
- Tangles appear as "flame-shaped" in pyramidal neurons (like those in hippocampus) or "globose" in other neuronal types
- The degree of cognitive impairment correlates with neurofibrillary tangle burden and distribution (Braak staging)