Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

“…As in most previous studies in this field (for review see [23]), our univariate analyses also documented a strong relationship between Braak NFT staging and cognition. This disagrees with the results of Scheff et al [59] who did not find any relationship between Braak NFT staging and cognition. The overrepresentation of intermediate Braak III stages in their sample is the most plausible explanation for this discrepancy.…”

“…This overall observation agrees with several earlier and recent contributions stressing the role of synapses in AD cognitive decline [8,18,28,42,43,58,59,68,71]. In particular, total numbers of spinophilin-immunoreactive puncta in the CA1 field and area 9 explain more than 20% and 60% of MMSE variability respectively.…”

“…Unusually high percentages of explained variability (18% for CA1 field and 39% for area 9) were also obtained when the CDR score was used as dependent variable. These values are comparable to those reported in our previous stereologic analysis of total NFT numbers in the CA1 field [75] but significantly higher than those found by Scheff et al [59] in respect to MMSE scores. As in most previous studies in this field (for review see [23]), our univariate analyses also documented a strong relationship between Braak NFT staging and cognition.…”

“…In line with this hypothesis, Scheff et al reported in the only stereologic study available in this field a weak positive relationship between NFT densities in layer II of the entorhinal cortex and loss of synaptic contacts in the outer molecular layer of dentate gyrus (i.e. 16% of the synaptic loss was explained by NFT densities), but failed to identify any relationship between the individual's Braak NFT staging and total synaptic numbers in this area [59]. However, this electron microscopy study did not specifically address postsynaptic changes and did not explore synaptic changes in CA1 field and neocortex.…”

“…The major hallmarks of AD include the presence of extracellular amyloid deposits and intracellular neurofibrillary tangles (NFT) [2,4,19,70,82]. Several studies have shown that in addition to these traditionally described lesions, AD is characterized by selective neuronal loss [30,72], severe and early loss of synapses [15,16,24,45,59], and synaptic pathology [41,44]. Early immunocytochemical studies indicated an average 45% decrease in presynaptic terminal density in the AD neocortex [44,45,76].…”