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1.  Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates 
Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal, and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging (MRI) usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum (CSP), signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces, and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology, and pathogenesis of CTE and Alzheimer’s disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP, and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.
doi:10.1111/j.1365-2990.2011.01186.x
PMCID: PMC3166385  PMID: 21696410
chronic traumatic encephalopathy; traumatic brain injuries; boxing; contact sports; Alzheimer’s disease; frontotemporal dementia; amyotrophic lateral sclerosis
2.  Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses 
ACS chemical biology  2009;4(8):673-684.
Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, showed conformation-dependent optical properties and could be utilized for ex vivo spectral assignment of distinct prion deposits from two mouse-adapted prion strains. p-FTAA also revealed staining of transient soluble pre-fibrillar non-thioflavinophilic Aβ- assemblies during in vitro fibrillation of Aβ peptides. In brain tissue samples, Aβ deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localization with conventional antibodies (6E10 and AT8), indicating that p-FTAA detects all the immuno-positive aggregated proteinaceous species in Alzheimer disease, but with significantly shorter imaging time (100 fold) compared to immunofluorescence. In addition, a patchy islet-like staining of individual Aβ plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA, suggesting that pre-fibrillar species are likely an intrinsic component of Aβ plaques in human brain. The major hallmarks of Alzheimer’s disease, namely Aβ aggregates versus NFTs could also be distinguished due to distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, Aβ−tau interactions and pathogenesis both ex vivo and in vivo.
doi:10.1021/cb900112v
PMCID: PMC2886514  PMID: 19624097
3.  Role of Vascular Risk Factors and Vascular Dysfunction in Alzheimer's Disease 
Recent findings indicate that vascular risk factors and neurovascular dysfunction play integral roles in the pathogenesis of Alzheimer's disease. In addition to aging, the most common risk factors for Alzheimer's disease are apolipoprotein e4 allele, hypertension, hypotension, diabetes, and hypercholesterolemia. All of these can be characterized by vascular pathology attributed to conditions such as cerebral amyloid angiopathy and subsequent blood-brain barrier dysfunction. Many epidemiological, clinical, and pharmacotherapeutic studies have assessed the associations between such risk factors and Alzheimer's disease and have found positive associations between hypertension, hypotension, and diabetes mellitus. However, there are still many conflicting results from these population-based studies, and they should be interpreted carefully. Recognition of these factors and the mechanisms by which they contribute to Alzheimer's disease will be beneficial in the current treatment regimens for Alzheimer's disease and in the development of future therapies. Here we discuss vascular factors with respect to Alzheimer's disease and dementia and review the factors that give rise to vascular dysfunction and contribute to Alzheimer's disease.
doi:10.1002/msj.20155
PMCID: PMC2918901  PMID: 20101718
Alzheimer's disease; apolipoprotein; blood-brain barrier; cholesterol; diabetes; hypertension; risk factors

Results 1-3 (3)