Question 1
A 74-year-old woman with a six-year history of gradually worsening episodic memory, followed by word-finding difficulty and getting lost in familiar places, dies and undergoes brain autopsy. Which pair of neuropathological findings would most strongly confirm that her dementia was caused by Alzheimer's disease?
💡 Hint
Look closely at: Alzheimer's disease · neuropathological findings
- A Extracellular amyloid-beta plaques and intracellular tau neurofibrillary tangles
- B Tau-positive Pick bodies with focal atrophy of the frontal and anterior temporal lobes
- C Intracellular alpha-synuclein Lewy bodies with loss of pigmented substantia nigra neurons
- D Multiple lacunar infarcts with diffuse ischemic damage to subcortical white matter
▸Show the answer — and why each of the other three is wrong
🔑 Key takeaway
Alzheimer's disease means amyloid-beta plaques outside neurons plus tau tangles inside them.
A is correct.Alzheimer's disease is defined neuropathologically by two hallmark lesions: extracellular amyloid-beta plaques, formed when amyloid precursor protein is cleaved into fragments that aggregate between neurons, and intracellular neurofibrillary tangles composed of hyperphosphorylated tau that has detached from microtubules. These lesions, together with synaptic and neuronal loss that typically begins in the entorhinal cortex and hippocampus, fit this patient's early episodic memory decline followed by language and visuospatial problems. Lewy bodies made of alpha-synuclein, with depletion of pigmented dopaminergic neurons in the substantia nigra, characterize Parkinson's disease and dementia with Lewy bodies, which typically present with fluctuating attention, recurrent visual hallucinations, and parkinsonism rather than a primarily amnestic course. Multiple lacunar infarcts with ischemic white matter damage point to vascular neurocognitive disorder, which more often shows a stepwise or patchy course with early slowing and executive dysfunction. Tau-positive Pick bodies with focal frontal and anterior temporal atrophy indicate a form of frontotemporal lobar degeneration, which usually begins with personality change, disinhibition, or language loss while memory is relatively spared. Although these conditions can coexist with Alzheimer's pathology, only plaques plus tangles confirm the Alzheimer's diagnosis.