Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer’s disease

Publication date: Available online 4 February 2017
Source:Neurobiology of Aging
Author(s): Zhiping Mi, Eric E. Abrahamson, Angela Y. Ryu, Kenneth N. Fish, Robert A. Sweet, Elliott J. Mufson, Milos D. Ikonomovic
Precuneus (PreC) cortex is affected with amyloid plaques early in Alzheimer's disease (AD), and this pathology may be associated with alterations in PreC synapses and cognitive impairment. We quantified spinophilin-immunoreactive (ir) dendritic spine density and intensity of spinophilin immunofluorescence, the latter as a measure of relative protein levels of spinophilin, in PreC lamina III from 33 subjects with clinical diagnoses of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild-moderate AD (mAD), or severe AD (sAD). Both measures of spinophilin were lower in mAD and sAD compared to NCI. The MCI group had higher relative protein levels of spinophilin compared to mAD and sAD, and higher spinophilin-ir dendritic spine density compared to sAD. Lower spinophilin-ir dendritic spine density and relative protein levels of spinophilin were associated with greater Aβ plaque burden, detected with a derivative of Pittsburgh compound-B (6-CN-PiB), and worse cognitive performance. Clinical onset of AD is marked by loss of PreC spinophilin-ir dendritic spines that is related to Aβ pathology and may contribute to cognitive symptoms early in the disease.



http://ift.tt/2jMkaQV