A 65-year-old woman is brought to the clinic by her husband due to worsening memory problems. She has a medical history significant for long-standing hypertension, type 2 diabetes mellitus, and depression. Physical examination shows cognitive impairment but no focal neurologic deficits. Two years later, the patient dies suddenly from a massive myocardial infarction. Congo red staining of brain samples obtained from the hippocampus and cerebral arterioles reveals patchy red deposits that turn yellow-green under polarized light. This patient most likely suffered from which of the following conditions?

Question

A 65-year-old woman is brought to the clinic by her husband due to worsening memory problems.  She has a medical history significant for long-standing hypertension, type 2 diabetes mellitus, and depression.  Physical examination shows cognitive impairment but no focal neurologic deficits.  Two years later, the patient dies suddenly from a massive myocardial infarction.  Congo red staining of brain samples obtained from the hippocampus and cerebral arterioles reveals patchy red deposits that turn yellow-green under polarized light.  This patient most likely suffered from which of the following conditions?

Quizplus · Accepted Answer

Amyloid is an abnormally folded (insoluble) fibrillar protein that deposits in the extracellular space of tissues. When stained with Congo red and viewed under polarized light, these deposits have a characteristic apple-green birefringence due to their β-sheet structure. Amyloid deposition can affect multiple organ systems, as occurs with plasma cell tumors (eg, amyloid light chain protein [AL]) and chronic inflammatory diseases (eg, amyloid-associated protein [AA]). However, in Alzheimer disease, amyloid deposits are seen exclusively in brain tissue. These deposits contain beta-amyloid (Aβ), which is formed by cleavage of amyloid precursor protein (a transmembrane glycoprotein). Early in the disease, neuritic (senile) plaques can be found in the medial temporal lobe (eg, hippocampus, amygdala, entorhinal cortex) and are composed of a central Aβ core surrounded by dystrophic neurites. Aβ deposition also occurs in the media/adventitia of cerebral vessels (amyloid angiopathy) and may cause vessel weakening with intracranial hemorrhage. (Choice B) Huntington disease typically presents with dementia, choreiform movements, dystonia, and psychiatric symptoms. Patients characteristically have atrophy of the caudate and microscopy reveals intranuclear inclusions containing aggregates of huntingtin protein. (Choice C) Parkinson disease usually presents with bradykinesia, rigidity, and tremor. Brain biopsy characteristically shows intracellular eosinophilic inclusions composed of α-synuclein (Lewy bodies). (Choice D) Pick disease (frontotemporal dementia) typically presents with changes in personality/behavior and abnormal speech (eg, aphasia). Individuals usually have pronounced frontotemporal brain atrophy, and silver staining shows round cytoplasmic inclusions containing aggregates of tau protein (Pick bodies). (Choice E) Elderly individuals may develop cognitive impairment in association with depression ("pseudodementia"); however, neuritic plaques and amyloid angiopathy would not be seen. (Choice F) Vascular dementia typically presents with sudden/stepwise cognitive decline in patients with cardiovascular risk factors and ischemic stroke. The absence of glial scar formation on autopsy makes vascular dementia less likely in this patient. (Choice G) Vitamin B₁₂ deficiency is common in the elderly and may cause dementia, peripheral neuropathy, and/or subacute combined degeneration; however, neuritic plaques and amyloid angiopathy would not be seen. Educational objective: Amyloid is an abnormally folded (insoluble) extracellular protein that has apple-green birefringence when stained with Congo red and viewed under polarized light. Alzheimer disease is associated with beta-amyloid deposits in the brain parenchyma (neuritic plaques) and walls of cerebral vessels (amyloid angiopathy). __________ References: Alzheimer's disease and the ß-amyloid peptide. (http://www.ncbi.nlm.nih.gov/pubmed/20061647)

A 65-Year-Old Woman Is Brought to the Clinic by Her