1. Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease
- Author
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Angela Y. Ryu, Elliott J. Mufson, Zhiping Mi, Milos D. Ikonomovic, Eric E. Abrahamson, Robert A. Sweet, and Kenneth N. Fish
- Subjects
0301 basic medicine ,Male ,Aging ,medicine.medical_specialty ,Dendritic spine ,Amyloid ,Amyloid beta ,Dendritic Spines ,Precuneus ,Nerve Tissue Proteins ,Plaque, Amyloid ,behavioral disciplines and activities ,Article ,White matter ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,Parietal Lobe ,mental disorders ,medicine ,Humans ,Cognitive Dysfunction ,Prefrontal cortex ,Aged, 80 and over ,Mini–Mental State Examination ,Amyloid beta-Peptides ,Aniline Compounds ,biology ,medicine.diagnostic_test ,General Neuroscience ,Microfilament Proteins ,Thiazoles ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology ,Pittsburgh compound B ,Neuroscience ,030217 neurology & neurosurgery ,Biomarkers ,Developmental Biology - Abstract
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 the spinophilin-immunoreactive (ir) dendritic spine density and the 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 with NCI. The MCI group had higher protein levels of spinophilin compared with mAD and sAD, and higher spinophilin-ir dendritic spine density compared with sAD. Lower spinophilin-ir dendritic spine density and relative protein levels of spinophilin were associated with greater amyloid beta (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 the loss of PreC spinophilin-ir dendritic spines that is related to Aβ pathology and may contribute to cognitive symptoms early in the disease.
- Published
- 2016