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

Neurobiol Aging. 2017 Jul;55:159-166. doi: 10.1016/j.neurobiolaging.2017.01.022. Epub 2017 Feb 4.


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.

Keywords: Amyloid; Default mode network; Episodic memory; Mild cognitive impairment; Synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds
  • Biomarkers / metabolism
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / etiology*
  • Dendritic Spines / metabolism*
  • Dendritic Spines / pathology*
  • Female
  • Humans
  • Male
  • Microfilament Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Parietal Lobe / metabolism*
  • Parietal Lobe / pathology*
  • Plaque, Amyloid / diagnosis
  • Plaque, Amyloid / metabolism
  • Thiazoles


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Biomarkers
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Thiazoles
  • neurabin