title: Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Abrahamson
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Ryu
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
authors.affiliation: Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: ikonomovicmd@upmc.edu.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D015415:Biomarkers / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000209:etiology*; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000175:diagnosis / Q000378:metabolism; D013844:Thiazoles; D000099273:Neurabins
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D013844:Thiazoles; D000099273:Neurabins; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
keywords: Amyloid; Default mode network; Episodic memory; Mild cognitive impairment; Synapse