Answer
Huntington disease (HD) is unique among the dementing illnesses in that it is always caused by a defect in a single gene, HTT. It is almost always autosomal dominant and, essentially, no sporadic form exists, although rare de novo mutations exist. HD is caused by a trinucleotide (CAG) repeat expansion in HTT that causes an elongated polyglutamine repeat in the Huntington protein. [24] Clinically, HD is primarily characterized by its characteristic choreiform movement disorder, but it also includes psychiatric disturbances and, ultimately, dementia. [25] No cure exists.
Pathologically, HD is characterized primarily by neuronal loss, atrophy, and gliosis of the caudate and putamen beginning in the anterior medial caudate. As the disease progresses, this neuronal loss, atrophy, and gliosis may involve multiple brain regions. Immunohistochemical staining against polyglutamine reveals intraneuronal inclusions, although this finding is usually not necessary for the diagnosis. Pathologic staging is performed by assessing the amount of atrophy, neuronal loss, and gliosis in the caudate and putamen. [26]
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Dementia pathology. Bielschowsky silver staining of the cortex at 400× magnification demonstrates a neurofibrillary tangle (black arrow) and a neuritic plaque (white arrow).
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Dementia pathology. Congo red staining of a small cortical artery at 400× magnification demonstrates salmon-colored amyloid deposition in the media of the vessel.
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Dementia pathology. A: Hematoxylin-eosin-Luxol fast blue staining of the basal ganglia at 100× magnification demonstrates a cavitary infarct. Calcific medial sclerosis of small arteries is also present. B: At 400× magnification, numerous foamy macrophages are present within the center of the infarcted tissue.
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Dementia pathology. A: Hematoxylin and eosin staining of the substantia nigra at 400× magnification demonstrates multiple Lewy bodies within a pigmented neuron. The Lewy bodies are round with a densely eosinophilic core surrounded by a clear halo. B: Immunohistochemical staining (brown) against alpha-synuclein at 400× magnification reveals a round Lewy body within the soma of a neuron.
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Dementia pathology. Comorbid brain pathologies are common in the elderly population. This Venn diagram demonstrates the co-occurrence of brain pathologies as evident from population-based autopsy studies of brain aging.
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Dementia pathology. A: Hematoxylin and eosin staining at 400× magnification of the dentate fascia of the hippocampus reveals round eosinophilic Pick bodies (arrows) in the soma of granular neurons. B: Immunohistochemical staining (brown) against tau at 400× magnification reveals round intraneuronal Pick bodies in cortical neurons.
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Dementia pathology. A: Hematoxylin and eosin staining at 400× magnification of the cerebral cortex reveals the coalescent clear vesicles characteristic of spongiform encephalopathy. B: Immunohistochemical staining (brown) against protease-resistant prion protein reveals the granular immunoreactivity seen in Creutzfeldt-Jakob disease.
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Dementia pathology. Immunohistochemical staining (brown) against tau at 400× magnification reveals glial immunoreactivity that is characteristic of this case of cortico-basal ganglionic degeneration.
