Pick's disease: a modern approach.

摘要

Pick's disease is a rare dementing disorder that is sometimes familial. The cardinal features are circumscribed cortical atrophy most often affecting the frontal and temporal poles and argyrophilic, round intraneuronal inclusions (Pick bodies). Clinical manifestations reflect the distribution of cortical degeneration, and personality deterioration and memory deficits are often more severe than visuospatial and apraxic disorders that are common in Alzheimer's disease, but clinical overlap with other non-Alzheimer degenerative disorders is increasingly recognized. Neuronal loss and degeneration are usually maximal in the limbic system, including hippocampus, entorhinal cortex and amygdala. Numerous Pick bodies are often present in the dentate fascia of the hippocampus. Less specific features include leukoencephalopathy and ballooned cortical neurons (Pick cells). Glial reaction is often pronounced in affected cerebral gray and white matter. Tau-immunoreactive glial inclusions are a recently recognized finding in Pick's disease, and neuritic changes have also recently been described. Variable involvement of the deep gray matter and the brainstem is typical, with a predilection for the monoaminergic nuclei and nuclei of the pontine base. Neurochemical studies demonstrate deficits in intrinsic cortical neurotransmitter systems (e.g., somatostatin), but inconsistent loss of transmitters in systems projecting to the cortex (e.g., cholinergic neurons of the basal nucleus). Biochemical and immunocytochemical studies have demonstrated that abnormal tau proteins are the major structural components of Pick bodies. A specific tau protein immunoblotting pattern different from that seen in Alzheimer's disease and certain other disorders has been suggested in some studies. A specific molecular marker and a genetic locus for familial cases are not known.