Neuropathology and applied neurobiology
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Neuropathol. Appl. Neurobiol. · Feb 2016
Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease.
Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ-aminobutyric acid (GABA)-ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. ⋯ We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease.
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Neuropathol. Appl. Neurobiol. · Dec 2015
Diagnostic accuracy of behavioral variant frontotemporal dementia consortium criteria (FTDC) in a clinicopathological cohort.
The aims of this study were to assess the sensitivity of the International Behavioural Variant FTD Criteria Consortium (FTDC) revised criteria of behavioural variant frontotemporal dementia (bvFTD) in a pathological cohort and to determine their predictive values in a clinical context suggestive of bvFTD. In addition, the study aimed to assess the influence of the age at onset and underlying pathology in the clinicopathological correlations. ⋯ The revised bvFTD criteria present good sensitivity and positive predictive value in both early- and late-onset cases and regardless of the underlying FTLD pathology.
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Neuropathol. Appl. Neurobiol. · Dec 2015
Early-onset axonal pathology in a novel P301S-Tau transgenic mouse model of frontotemporal lobar degeneration.
Tau becomes hyperphosphorylated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-tau), resulting in functional deficits of neurones, neurofibrillary tangle (NFT) formation and eventually dementia. Expression of mutant human tau in the brains of transgenic mice has produced different lines that recapitulate various aspects of FTLD-tau and AD. In this study, we characterized the novel P301S mutant tau transgenic mouse line, TAU58/2. ⋯ In TAU58/2 mice, early tau pathology induces functional deficits of neurones associated with NF pathology. This appears to be specific to tau, as similar changes are observed in FTLD-tau, but not in FTLD with TDP-43 inclusions. Therefore, TAU58/2 mice recapitulate aspects of human FTLD-tau and AD pathology, and will become instrumental in studying disease mechanisms and therapeutics in the future.
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Neuropathol. Appl. Neurobiol. · Oct 2015
ReviewMolecular and cellular pathogenesis of adamantinomatous craniopharyngioma.
Adamantinomatous craniopharyngiomas (ACPs) are the most common pituitary tumours in children. Although histologically benign, these are clinically aggressive tumours, difficult to manage and associated with poor quality of life for the patients. ⋯ As the result of this basic research, the pathogenesis of ACP is being unveiled, with promising implications for the development of novel treatments against these childhood neoplasms. These benign tumours may additionally represent a unique model to provide insights into the initial steps of oncogenesis.
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Neuropathol. Appl. Neurobiol. · Feb 2015
ReviewInvited review: Neuropathology of tauopathies: principles and practice.
Tauopathies are clinically, morphologically and biochemically heterogeneous neurodegenerative diseases characterized by the deposition of abnormal tau protein in the brain. The neuropathological phenotypes are distinguished based on the involvement of different anatomical areas, cell types and presence of distinct isoforms of tau in the pathological deposits. The nomenclature of primary tauopathies overlaps with the modern classification of frontotemporal lobar degeneration. ⋯ In addition, further neurodegenerative conditions with diverse aetiologies may be associated with tau pathologies. Thus, the spectrum of tau pathologies and tauopathy entities expands beyond the traditionally discussed disease forms. Detailed multidisciplinary studies are still required to understand their significance.