Article

DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 27: 457-464

University of Kentucky, Lexington, Kentucky, United States
Annals of Neurology (Impact Factor: 9.98). 05/1990; 27(5):457-64. DOI: 10.1002/ana.410270502
Source: PubMed

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)

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    • "An early characteristic of the Alzheimer's brain is the loss of synapses and this occurs prior to memory loss. Synapse density therefore provides a better correlate with cognitive deficits than the classic hallmarks of plaques or tangles (DeKosky and Scheff, 1990;Terry et al., 1991). A study of pre-symptomatic AD mice (i.e. "
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    • "Histopathologic hallmarks of AD are represented by (i) focal extracellular deposits of fibrillar b-amyloid (Ab), also known as senile or neuritic plaques, and (ii) intraneuronal accumulation of neurofibrillary tangles composed of filamentous aggregates of hyperphosphorylated Tau protein (Selkoe, 2001). The degeneration and loss of synapses precedes neuronal death (DeKosky and Scheff, 1990; Scheff et al., 1991) and may account for early cognitive impairment. It is believed that neurodegeneration occurs gradually and dementia represents the end stage of accumulating pathologic changes that may start to develop decade(s) before the onset of the earliest clinical symptoms (Jack et al., 2010). "
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