Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68: 1501-1508

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Neurology (Impact Factor: 8.29). 06/2007; 68(18):1501-8. DOI: 10.1212/01.wnl.0000260698.46517.8f
Source: PubMed


To evaluate the total number of synapses in the stratum radiatum (str rad) of the human hippocampal CA1 subfield in individuals with mild Alzheimer disease (mAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI) and determine if synapse loss is an early event in the progression of the disease.
Short postmortem autopsy tissue was obtained, and an unbiased stereologic sampling scheme coupled with transmission electron microscopy was used to directly visualize synaptic contacts.
Individuals with mAD had fewer synapses (55%) than the other two diagnostic groups. Individuals with MCI had a mean synaptic value that was 18% lower than the NCI group mean. The total number of synapses showed a correlation with several cognitive tests including those involving both immediate and delayed recall. Total synaptic numbers showed no relationship to the subject's Braak stage or to APOE genotype. The volume of the str rad was reduced in mAD vs the other two diagnostic groups that were not different from each other.
These results strongly support the concept that synapse loss is a structural correlate involved very early in cognitive decline in mild Alzheimer disease (mAD) and supports mild cognitive impairment as a transitional stage between mAD and no cognitive impairment.

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    • "t al . , 1991 ) . Synapse loss affects different neuronal populations and neurotransmitter systems in brains of AD subjects ( Masliah et al . , 1990 ; Scheff et al . , 1990 , 2007 ) . Individuals with amnestic MCI and AD have significantly fewer synapses and synaptic proteins in CA1 hippocampus and inferior temporal and posterior cingulate gyrus ( Scheff et al . , 2007 ) . Accumulation of soluble toxic forms of tau and Aβ at synapses may be a crucial event leading to synapse loss and neurodegeneration ( Spires - Jones and Hyman , 2014 ) . Thus , loss of dendritic spines in cortical pyramidal neurons parallels tau phosphorylation during aging ( Merino - Serrais et al . , 2013 ) , whereas soluble Aβ pep"
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    • "Neurofibrillary tangles, amyloid plaques, neuronal loss and synaptic failure represent the major hallmarks of Alzheimer's disease (AD; Wischik et al., 1988; Rinne et al., 1989; DeKosky and Scheff, 1990; Cras et al., 1991; West et al., 1994; Coleman and Yao, 2003). Synaptic deficits occur very early in AD and correlate well with the severity of dementia in AD patients (Davies et al., 1987; Masliah et al., 2001; Scheff et al., 2007). "
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    • "The lack of GPR84 increases b-amyloid-induced dendritic degeneration It is known that b-amyloid induces dendritic degeneration in APP/PS1 mice (Tsai et al., 2004; Dikranian et al., 2012) and AD brains (Masliah et al., 1994; Scheff et al., 2007), but whether microglia exert a protective or deleterious role in this phenomenon is still a matter of speculation (Siskova and Tremblay, 2013). To assess whether microglial GPR84 influences dendritic degeneration , we examined the hippocampal CA1 stratum radiatum of Fig. 2. Clinical assessment of GPR84 knockout and wild-type mice in three disease models. "
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