Developmental deficits and staging of dynamics of age associated Alzheimer's disease neurodegeneration and neuronal loss in subjects with Down syndrome.

The increased life expectancy of individuals with Down syndrome (DS) is associated with increased prevalence of trisomy 21-linked early-onset Alzheimer's disease (EOAD) and dementia. The aims of this study of 14 brain regions including the entorhinal cortex, hippocampus, basal ganglia, and cerebellum in 33 adults with DS 26-72 years of age were to identify the magnitude of brain region-specific developmental neuronal deficits contributing to intellectual deficits, to apply this baseline to identification of the topography and magnitude of neurodegeneration and neuronal and volume losses caused by EOAD, and to establish age-based staging of the pattern of genetically driven neuropathology in DS. Both DS subject age and stage of dementia, themselves very strongly correlated, were strong predictors of an AD-associated decrease of the number of neurons, considered a major contributor to dementia.

Clinicopathological Staging of Dynamics of Neurodegeneration and Neuronal Loss in Alzheimer Disease.

Clinical and neuropathological staging of Alzheimer disease (AD) neurodegeneration and neuronal loss dynamics is the baseline for identification of treatment targets and timing. The aim of this study of 14 brain regions in 25 subjects diagnosed with AD and 13 age-matched control subjects was to establish the pattern of neurodegeneration, and the severity and rate of neuronal loss in mild cognitive impairment/mild AD (Functional Assessment Staging [FAST] test 3-4), moderate to moderately severe AD (FAST 5-6), and severe AD (FAST 7). The study revealed (1) the most severe neuronal loss in FAST 3-4; (2) the highest rate of neuronal loss in FAST 5-6, to the "critical" point limiting further increase in neuronal loss; (3) progression of neurofibrillary degeneration, but decline of neuronal loss to a floor level in FAST 7; and (4) structure-specific rate of neuronal loss caused by neurofibrillary degeneration and a large pool of neuronal loss caused by other mechanisms.

Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects.

Introduction: In autism spectrum disorder, lack of coherence and of complex information processing, and narrowly focused interests and repetitive behaviors are considered a sign of long-range underconnectivity and short-range overconnectivity. The goal of this morphometric study of five anatomically and functionally different segments of the corpus callosum (CC) was to establish patterns of differences between long-range interhemispheric connections in nine neurotypical and nine autistic subjects.

Results: Electron microscopy revealed a significant reduction in average axon diameter and axon cross-sectional area in autistic subjects, and reduction in CC segment-specific diversification of connections of functionally different cortical regions.

The role of reduced expression of fragile X mental retardation protein in neurons and increased expression in astrocytes in idiopathic and syndromic autism (duplications 15q11.2-q13).

Fragile X syndrome (FXS), caused by lack of fragile X mental retardation protein (FMRP), is associated with a high prevalence of autism. The deficit of FMRP reported in idiopathic autism suggests a mechanistic overlap between FXS and autism. The overall goal of this study is to detect neuropathological commonalities of FMRP deficits in the brains of people with idiopathic autism and with syndromic autism caused by dup15q11.

Multiregional Age-Associated Reduction of Brain Neuronal Reserve Without Association With Neurofibrillary Degeneration or β-Amyloidosis.

Increase in human life expectancy has resulted in the rapid growth of the elderly population with minimal or no intellectual deterioration. The aim of this stereological study of 10 structures and 5 subdivisions with and without neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was to establish the pattern of age-associated neurodegeneration and neuronal loss in the brains of nondemented adults and elderly. The study revealed the absence of significant neuronal loss in 7 regions and topographically selective reduction of neuronal reserve over 77 years in 8 brain structures including the entorhinal cortex (EC) (-33.