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Chronic traumatic encephalopathy
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Recently, as part of a National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Biomedical Imaging and Bioengineering (NIBIB) funded initiative, a panel of expert neuropathologists evaluated 25 cases of various tauopathies blinded to all clinical, demographic, and gross neuropathological information. The tauopathies included examples of CTE, AD, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy (PART), and GPDC. A single laboratory processed all cases uniformly, and the resulting slides were scanned into digital images that were provided to neuropathologists blinded to all other information. The evaluating neuropathologists submitted their independent evaluations prior to a face-to-face meeting.
Clinical development of passive tau-based immunotherapeutics for treating primary and secondary tauopathies
Published in Expert Opinion on Investigational Drugs, 2023
Francesco Panza, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Nicoletta Cirillo, Christian Damiani, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Madia Lozupone
The presence of increased brain deposition of insoluble aggregates of hyperphosphorylated tau protein may not always be associated with and diagnosed as a disease process. Currently, we recognize three main age-related tauopathies: primary age-related tauopathy (PART) [12], aging-related tau astrogliopathy (ARTAG) [13], and argyrophilic grain disease (AGD) [14]. PART has been recently proposed as a condition characterized by neuronal deposits of protein tau in brain limbic structures, without or with a minimal presence of Aβ deposits [12]. However, PART may represent a distinct entity, a prodromal phase of AD [15] or, alternatively, a putative cause of cognitive impairment in subjects with suspected non-Alzheimer’s disease pathophysiology (SNAP), with altered tau biomarkers and positive clinical AD criteria and without significant Aβ biomarkers [16]. ARTAG is characterized by tau protein deposits in thorny and granular astrocytes, and these neuropathological lesions are different from the astroglial lesions of primary tauopathies [13]. This neuropathological pattern of tau astrogliopathy was found in subpial, subependymal, or perivascular spaces, and primarily in the medial temporal lobe/amygdala [17]. Currently, ARTAG may be a prodromal phase of other tauopathies, although there is no clinical characterization of this condition [18]. Finally, AGD has no clinical correlates [5] and presents silver-positive grain-like structures particularly in the medial temporal lobe [14]. Therefore, whether this neuropathological condition may be considered a neurodegenerative disease is unclear.
Chronic traumatic encephalopathy in sports: a historical and narrative review
Published in Developmental Neuropsychology, 2018
What is tau? Tau is a protein that fortifies microtubules in neurons, and everyone has it. Tau is the structural support that holds the components of the neuron together. When tau breaks down, so does the microtubule, and the neuron falls apart and dies, degenerating into hyperphosphorylated tau, known as p-tau. According to Karantzoulis and Randolph (2013), there are many tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA), and others. Neuropathologist Rudy Castellani, at the Soccer Summit held in New York in 2017 (Castellani, 2017), commented that p-tau (“tauopathy”) is a secondary accumulation in many conditions, including… “Life on earth…life itself it a progressive tauopathy.” The Alzheimer’s literature offers a valuable insight about abnormal tau development across the lifespan. Braak, Thal, Ghebremedhin, and Del Tredici (2011) reported on abnormal tau pathology in 2,332 consecutive, unselected autopsies, ages 1–100. Braak et al. (2011) reported that only 10 of 2,332 (0.004%) were negative for any abnormal tau, and all were < 30 years of age. By about age 24, there was some degree of abnormal tau in nearly all patients. It should be mentioned, however, that the NINDS CTE Neuropathology Consensus group (McKee et al., 2016) identified p-tau in a specific region and pattern, and stated that the p-tau of CTE was different from the age-related tau astrogliopathy (ARTAG) or primary age-related tauopathy (PART), presumably noted by Braak (2011).
Recent developments with tau-based drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Khalid Iqbal, Fei Liu, Cheng-Xin Gong
In addition to AD, tau pathology is a hallmark of a number of related neurodegenerative disorders, called tauopathies, which include frontotemporal dementia, progressive supra nuclear palsy, corticobasal degeneration, Pick’s disease, traumatic chronic encephalopathy/dementia pugilistica, argophylic grain disease, and Guam Parkinsonism dementia complex. Certain mutations in tau cause frontotemporal dementia and progressive supra nuclear palsy [19–21]. As many as 20% of all aged individuals have tau pathology, but no Aβ pathology in the brain, and they were recently named primary age-related tauopathy (PART) [22,23].The pathology in PART is mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas. Tau pathology in different tauopathies show different morphologies, but without exception they are made up of hyperphosphorylated tau. Interestingly, in AD a similar pattern of hyperphosphorylation as in other tauopathies is seen but in the absence of any tau mutation. Thus, tau pathology can be a primary as in PART and frontolobar dementias and a secondary cause of the disease as in AD. In this article, we discuss the rationale and the promise of recent developments in tau-based drug discovery.