What is Pick's disease characterized by the presence of Pick bodies in the brain of an elderly patient?

Pick's Disease with Pick Bodies

Pick's disease is a rare frontotemporal lobar degeneration (FTLD-tau) characterized by circumscribed frontal and temporal lobe atrophy with distinctive argyrophilic, round intraneuronal tau-positive inclusions called Pick bodies, presenting clinically as progressive behavioral and executive dysfunction with personality changes. 1

Neuropathological Features

Pick bodies are the pathological hallmark and consist of abnormal tau proteins that form round, argyrophilic intraneuronal inclusions, predominantly containing three microtubule-binding repeat tau isoforms (though four-repeat isoforms can also be present). 1, 2, 3

Key Pathological Characteristics:

• Circumscribed cortical atrophy affecting frontal and temporal poles most severely 1
• Pick bodies are tau-positive, ubiquitin-positive inclusions found abundantly in the dentate fascia of the hippocampus, limbic system, entorhinal cortex, and amygdala 1, 4
• Pick cells (ballooned neurons) with chromatolysis in affected cortical regions 1, 5
• Pan-laminar neuronal loss most severe in layers II-III of the cortex with pronounced gliosis 1, 5
• Leukoencephalopathy with white matter degeneration 1
• Tau-immunoreactive glial inclusions including coiled bodies and thorned astrocytes 5, 3

Biochemical Signature:

The 55 and 64 kDa tau protein doublet on Western blot is specific to Pick's disease, distinguishing it from Alzheimer's disease (which shows a 55,64,69 kDa triplet) and progressive supranuclear palsy (which shows a 64,69 kDa doublet). 2

Clinical Presentation

The clinical syndrome manifests as progressive dysexecutive and behavioral changes with personality deterioration, disinhibition, apathy, and repetitive/compulsive behaviors, while visuospatial abilities and memory are relatively preserved early in the disease course. 6, 7, 1

Clinical Features:

• Age of onset typically between 48-65 years (presenile period), rare after age 75 7
• Executive dysfunction with impaired judgment, problem-solving, and reasoning 6
• Personality and behavioral changes including disinhibition, apathy, loss of empathy, and compulsive behaviors 6, 5
• Language impairment may develop, particularly non-fluent or semantic variant primary progressive aphasia 6
• Memory relatively spared early compared to Alzheimer's disease 1
• Progressive course over years leading to mutism and vegetative state 5

Diagnostic Approach

The diagnosis requires clinical identification of a progressive dysexecutive/behavioral syndrome combined with neuroimaging showing characteristic frontal and temporal atrophy, followed by exclusion of alternative etiologies. 7

Neuroimaging:

• MRI brain without contrast is the primary imaging modality showing progressive bilateral frontal and temporal lobe atrophy 6, 7, 5
• FDG-PET/CT demonstrates hypometabolism in frontal and/or temporal regions, helping differentiate from Alzheimer's disease with 60% sensitivity and 78.5% positive predictive value 7

Differential Diagnosis:

Pick's disease must be distinguished from other causes of progressive dysexecutive/behavioral syndromes:

• Alzheimer's disease (most common alternative) 6
• Other FTLD pathologies including FTLD-TDP43, progressive supranuclear palsy, and corticobasal degeneration 6, 8
• Lewy body disease 6
• Vascular contributions to cognitive impairment 6

Diagnostic Limitations:

Definitive diagnosis requires neuropathological confirmation showing Pick bodies, obtainable only through biopsy or autopsy; clinical diagnosis represents the most likely etiology, not pathological certainty. 7 Many neuropathologists consider FTLD-tau to include Pick's disease, progressive supranuclear palsy, and corticobasal degeneration as related entities. 6

Management Considerations

Serial clinical assessments and repeat neuroimaging help confirm the progressive nature and refine diagnosis over time, documenting progression of cognitive, behavioral, and functional decline. 7

Referral to a dementia specialist is recommended if diagnostic uncertainty persists, and genetic counseling should be offered if autosomal dominant family history is present, as Pick's disease can be familial in some cases. 7, 1

Clinical Pitfalls:

• Do not rely solely on clinical presentation, as significant overlap exists between Pick's disease and other frontotemporal dementias 6
• Pick's disease can coexist with other pathologies (e.g., progressive supranuclear palsy), complicating the clinical picture 5
• TDP-43 inclusions may be present in some Pick's disease cases, suggesting heterogeneous pathways of disease development 4