Synapse loss in frontal cortex in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 27: 457-464
ABSTRACT Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, less than 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED AT 250 WORDS)
- SourceAvailable from: Santosh Jadhav
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- "Structural and functional synaptic changes are observed in both early and late stages of AD (Sze et al., 2000; Masliah et al., 2001; Honer, 2003; Reddy et al., 2005; Counts et al., 2006). Moreover, these changes correlate well with the cognitive decline in AD (DeKosky and Scheff, 1990; Braak and Braak, 1991; Arriagada et al., 1992; Blennow et al., 1996; Callahan et al., 2002). The synaptic damage is characterized by deregulation of synaptic proteins at the protein and mRNA levels (Coleman and Yao, 2003; Honer, 2003; Tao et al., 2003). "
ABSTRACT: Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer's disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model of tauopathy that develops extensive neurofibrillary pathology in the cortex. Using fractionation of cortical synapses, we identified an increase in endogenous rat tau isoforms in presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD). Truncated transgenic tau was distributed in both compartments exhibiting specific phospho-pattern that was characteristic for each synaptic compartment. In the presynaptic compartment, truncated tau was associated with impairment of dynamic stability of microtubules which could be responsible for reduction of synaptic vesicles. In the PSD, truncated tau lowered the levels of neurofilaments. Truncated tau also significantly decreased the synaptic levels of Aβ40 but not Aβ42. These data show that truncated tau differentially deregulates synaptic proteome in pre-and postsynaptic compartments. Importantly, we show that alteration of Aβ can arise downstream of truncated tau pathology.Frontiers in Cellular Neuroscience 02/2015; 9(24). DOI:10.3389/fncel.2015.00024 · 4.18 Impact Factor
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- "Astroglial atrophy may be directly linked to a reduction of astroglial homeostatic support, which may have dire consequences for performance and survival of neurones as well as may affect functional activity of synapses. All of this can result in trimming synaptic contacts, affecting transmission and weakening synaptic plasticity, which are precisely the early pathological events observed in AD (Terry, 2000; Coleman et al., 2004); a decrease in synaptic densities has been reported to correlate with the severity of dementia (DeKosky and Scheff, 1990; Samuel et al., 1994). Astrocytes support synaptic transmission through multiple mechanisms (Verkhratsky and Nedergaard, in press). "
ABSTRACT: Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contribute to the ageing of the brain and to neurodegenerative diseases. Changes in astroglia in ageing and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter homeostatic reserve of the brain and contribute to early cognitive deficits. At the later stages of AD reactive astrocytes are associated with neurite plaques, the future commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortex astrocytes to not mount gliotic response to emerging β-amyloid deposits. This deficits in reactivity coincides with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at prevention and cure of neurodegenerative disorders. Copyright © 2015. Published by Elsevier Ltd.Neuroscience 01/2015; DOI:10.1016/j.neuroscience.2015.01.007 · 3.33 Impact Factor
- "Despite a great number of ongoing investigations , many neurodegenerative diseases or injury of the nervous system remain incurable. The fundamental structural problem in the patients with neurodegenerative diseases is damage of nerve cells, subsequently destruction and dysfunction of the neural networks (DeKosky and Scheff, 1990; Jackson et al., 1995; Liberski and Budka, 1999; Mattila et al., 1999). Prevention of the cell damage and promotion of axonal regeneration and neural network reconstruction would be the essential steps in the fundamental recovery of brain function. "
Article: Neuroprotection by Saponins[Show abstract] [Hide abstract]
ABSTRACT: Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones. Their diverse biological activities are ascribed to their different structures. Saponins have long been recognized as key ingredients in traditional Chinese medicine. Accumulated evidence suggests that saponins have significant neuroprotective effects on attenuation of central nervous system disorders, such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, our understanding of the mechanisms underlying the observed effects remains incomplete. Based on recently reported data from basic and clinical studies, this review highlights the proposed mechanisms of their neuroprotective function including antioxidant, modulation of neurotransmitters, anti-apoptosis, anti-inflammation, attenuating Ca2+ influx, modulating neurotrophic factors, inhibiting tau phosphorylation, and regeneration of neural networks. Copyright © 2014 John Wiley & Sons, Ltd.Phytotherapy Research 11/2014; 29(2). DOI:10.1002/ptr.5246 · 2.40 Impact Factor