55 year old farmer presents with a 2 year history of cognitive decline that initially started with depression, reduced speech, difficulty operating machinery, myoclonus and limb stiffness. CSF results show p-tau 129 (normal less than 75), t-tau 923 (normal less than 357), ABeta1-42 of 529 (normal more than 603).
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Moderate biparietal and left frontotemporal atrophy with relative preservation of hippocampi. Mild atrophy of left basal ganglia structure with bilateral T2 subcortical hyperintensities.
SPECT Tc-99 displaying decreased metabolism
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Bilateral hypometabolism in the frontal, parietal and temporal lobes with left-side and anterior predominance.
Tau protein is an important component in the assembly of neuronal microtubules, which facilitates intraneuronal transporting. In Alzheimer's disease (AD), tau protein is hyperphosphorylated (p-tau) and , histiologically, aggregated in neurofibrillary tangles1. The hyperphosphorylation of tau exists in a variety of dementia and movement disorders, and these are subsumed under 'tauopathies'. It can also co-exist with amyloid depositions. In clinical practice, the distinction of pathological, clinical and radiological finding can be complex, as findings may overlap.
This man presents to various health services with a range of symptoms consisted of limb apraxia, non-fluent aphasia, frontal behaviour changes, myoclonus, visuospatial deficits, depression to extrapyramidal symptoms. He has attracted various cross-sectional diagnoses of AD, progressive non-fluent/agrammatic aphasia(PNFA) and Dementia with Lewy Body(DLB). However, the initial presentation and the course of the disease suggest corticobasal degeneration (CBD)2. Clinically, CBD may present like DLB. For example, such patients may present with extrapyramidal symptoms, mood disorders and cognitive decline. Frontotemporal Dementia, PNFA, AD and CBD lies in the spectrum of tauopathies. Radiology findings of tauopathies can be unspecific and not correlate with the clinical phenotype, as demonstrated in the SPECT scan of this case. Novel tau-specific PET tracers or ligands are available in the research settings and may potentially be useful in determining subtypes of tauopathies3.
In such cases where the cross-sectional presentation differs over time, a cerebrospinal fluid investigation can increase the accuracy of diagnosis. Although the Amyloid/p-tau ratio in our case is consistent with late-onset Alzheimer's, the patient presents with early onset dementia and the CSF tau is disproportionately greater than amyloid4.
Coincidentally, this man has a history of significant head injury, which may have contributed to the course of his tau dementia. However, the association between tau and head injury remains debatable, and neuropathological examination is the current gold-standard for diagnosis tau-related dementia that is due to chronic traumatic encephalopathy5.
- 1. Iqbal K et al. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016 Jan;12(1):15-27.
- 2. Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80(5):496-503.
- 3. Saint-Aubert L et al. Tau PET imaging: present and future directions. Molecular Neurodegeneration. 2017;12:19.
- 4. Skillbäck T et al. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia. Brain. 2015 Sep;138(Pt 9):2716-31.
- 5. McKee AC, Cairns NJ, Dickson DW, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathologica. 2016;131:75-86.