Answer
Frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are characterized clinically by early onset (usually sixth and seventh decade of life), loss of executive function, disrupted language and motor function, and relative sparing of memory and visuospatial functions. [9] Pathologically, they have variable atrophy of the frontal and temporal lobes that is often asymmetric. FTDs are heterogenous with multiple etiologies, and many have characteristic histopathologic changes. [23]
Pick disease is probably the most well-known of the FTDs and is characterized by widespread presence of spherical intraneuronal Pick bodies that are positive for microtubule-associated protein tau (MAPT), as well as other proteins (see the image below). Pick bodies may also be identified using silver staining techniques such as Bielschowsky or Gallyas.
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.
One FTD characterized by the presence of ubiquitin-positive inclusions (FTD-U) occurs as part of a disease spectrum with motor neuron disease. A familial form of FTD, FTD with parkinsonism linked to chromosome 17, was later found to map to the MAPT locus and has characteristic tau pathology. Multiple other FTDs exist; some have characteristic neuronal inclusions (eg, neurofilament, TAR DNA binding protein-43), whereas others lack distinctive histopathologic changes. Single gene defects have been identified for many FTDs, including PGRN, FUS, CHMP2B, and VCP. The prevalence of FTD is low, and the population prevalence of sporadic and genetic disease is not known.
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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.
