"There is emerging evidence that biomarkers, including brain imaging markers, represent prodromal characteristics that anticipate Alzheimer's disease, Huntington's disease, and Parkinson's disease (Aylward, Liu, Nopoulos, Ross, Pierson, Mills, Long, & Paulsen, 2012; Lo, Hubbard, Shaw, Trojanowski, Petersen, Aisen, Weiner, & Jagust, 2011; Rodriguez- Oroz, Jahanshahi, Krack, Litvan, Macias, Bezard, & Obeso, 2009; Tabrizi, Scahill, Durr, Roos, Leavitt, Jones, Landwehrmeyer, Fox, Johnson, Hicks, Kennard, Craufurd, Frost, Langbehn, Reilmann, & Stout, 2011). Prevention science and/or interventions designed to attenuate the progression of symptoms holds much promise for these conditions (Rosenberg, 2011; Schapira & Tolosa et al., 2010). In the current study, we present preliminary evidence that a brain imaging marker collected at 6 months of age predicts the performance level of an important social-cognitive behavior at 9 months of age. "
[Show abstract][Hide abstract] ABSTRACT: Elucidating the neural basis of joint attention in infancy promises to yield important insights into the development of language and social cognition, and directly informs developmental models of autism. We describe a new method for evaluating responding to joint attention performance in infancy that highlights the 9- to 10-month period as a time interval of maximal individual differences. We then demonstrate that fractional anisotropy in the right uncinate fasciculus, a white matter fiber bundle connecting the amygdala to the ventral-medial prefrontal cortex and anterior temporal pole, measured in 6-month-olds predicts individual differences in responding to joint attention at 9 months of age. The white matter microstructure of the right uncinate was not related to receptive language ability at 9 months. These findings suggest that the development of core nonverbal social communication skills in infancy is largely supported by preceding developments within right lateralized frontotemporal brain systems.
[Show abstract][Hide abstract] ABSTRACT: Dementias are the most common neurodegenerative diseases and they are increasingly becoming a major public health problem. The most common form of dementia, affecting over 20 million people worldwide, is Alzheimer’s disease (AD). AD is a neurodegenerative disease of the central nervous system mainly found in older adults, with an incidence that increases with age. With the development of newer technologies, including genetic screening technologies and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined; indeed, these approaches are able to provide support not only in the clinical diagnosis of dementia, but also in its presymptomatic evaluation. Many researchers agree that early identification of AD, before abnormal accumulation of amyloid and tau proteins, could provide an opportunity to hinder the progression of the disease. [18F]2-fluoro-2-deoxy-d-glucose (FDG) PET studies have shown that decreased glucose metabolism in AD precedes clinical diagnosis and that the degree of clinical disability in AD correlates closely with the magnitude of the reduction in brain glucose metabolism. Data on presymptomatic mutation carriers from families with known early-onset autosomal dominant AD (familial AD) show reductions in the cerebral metabolic rate of glucose (CMRglc), consistent with the expected AD PET pattern, in the absence of severe atrophy on MRI. These results suggest that PET CMRglc measures have the potential to serve as preclinical biomarkers of dementia, useful also for tracking disease progression. This review highlights the role of genetics and FDG PET in understanding the pathogenesis of dementia.
[Show abstract][Hide abstract] ABSTRACT: Low-density lipoprotein receptor-related protein-1 (LRP1) is the main cell surface receptor involved in brain and systemic clearance of the Alzheimer's disease (AD) toxin amyloid-beta (Aβ). In plasma, a soluble form of LRP1 (sLRP1) is the major transport protein for peripheral Aβ. LRP1 in brain endothelium and mural cells mediates Aβ efflux from brain by providing a transport mechanism for Aβ across the blood-brain barrier (BBB). sLRP1 maintains a plasma 'sink' activity for Aβ through binding of peripheral Aβ which in turn inhibits re-entry of free plasma Aβ into the brain. LRP1 in the liver mediates systemic clearance of Aβ. In AD, LRP1 expression at the BBB is reduced and Aβ binding to circulating sLRP1 is compromised by oxidation. Cell surface LRP1 and circulating sLRP1 represent druggable targets which can be therapeutically modified to restore the physiological mechanisms of brain Aβ homeostasis. In this review, we discuss how increasing LRP1 expression at the BBB and liver with lifestyle changes, statins, plant-based active principles and/or gene therapy on one hand, and how replacing dysfunctional plasma sLRP1 on the other regulate Aβ clearance from brain ultimately controlling the onset and/or progression of AD.
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