PMID- 25756588
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20181113
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 74
IP  - 4
DP  - 2015 Apr
TI  - Hippocampal endosomal, lysosomal, and autophagic dysregulation in mild cognitive 
      impairment: correlation with abeta and tau pathology.
PG  - 345-58
LID - 10.1097/NEN.0000000000000179 [doi]
AB  - Endosomal-lysosomal and autophagic dysregulation occurs in the hippocampus in 
      prodromal Alzheimer disease (AD), but its relationship with beta-amyloid (Abeta) and 
      tau pathology remains unclear. To investigate this issue, we performed immunoblot 
      analysis of hippocampal homogenates from cases with an antemortem clinical 
      diagnosis of no cognitive impairment, mild cognitive impairment (MCI), and AD. 
      Western blot analysis revealed significant increases in the acid hydrolase 
      cathepsin D and early endosome marker rabaptin5 in the MCI group compared with 
      AD, whereas levels of phosphorylated mammalian target of rapamycin proteins 
      (pmTOR), total mammalian target of rapamycin (mTOR), p62, traf6, and LilrB2 were 
      comparable across clinical groups. Hippocampal Abeta1-40 and Abeta1-42 concentrations 
      and AT8-immunopositive neurofibrillary tangle density were not significantly 
      different across the clinical groups. Greater cathepsin D expression was 
      associated with global cognitive score and episodic memory score but not with 
      mini mental state examination or advanced neuropathology criteria. These results 
      indicate that alterations in hippocampal endosomal-lysosomal proteins in MCI are 
      independent of tau or Abeta pathology.
FAU - Perez, Sylvia E
AU  - Perez SE
AD  - From the Department Neurological Science, Rush University Medical Center, 
      Chicago, Illinois (SEP, EJM); Alzheimer's Disease Research Laboratory, Barrow 
      Neurological Institute, Phoenix, Arizona (BH, MN, EJM); Department of Neurology, 
      University of Miami Miller School of Medicine, Miami, Florida (JW); Center for 
      Dementia Research, Nathan Kline Institute, Orangeburg, New York (SDG); and 
      Departments of Psychiatry, Physiology and Neuroscience, NYU Langone Medical 
      Center, New York (SDG), New York; and Departments of Neurology and Psychiatry, 
      University of Pittsburgh and Geriatric Research Education and Clinical Center, VA 
      Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (MDI).
FAU - He, Bin
AU  - He B
FAU - Nadeem, Muhammad
AU  - Nadeem M
FAU - Wuu, Joanne
AU  - Wuu J
FAU - Ginsberg, Stephen D
AU  - Ginsberg SD
FAU - Ikonomovic, Milos D
AU  - Ikonomovic MD
FAU - Mufson, Elliott J
AU  - Mufson EJ
LA  - eng
GR  - R01 AG042210/AG/NIA NIH HHS/United States
GR  - P01AG14449/AG/NIA NIH HHS/United States
GR  - P01AG107617/AG/NIA NIH HHS/United States
GR  - R01 AG043375/AG/NIA NIH HHS/United States
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - P01 AG014449/AG/NIA NIH HHS/United States
GR  - R01AG043375/AG/NIA NIH HHS/United States
GR  - P01 AG017617/AG/NIA NIH HHS/United States
GR  - P30AG010161/AG/NIA NIH HHS/United States
GR  - P01 AG025204/AG/NIA NIH HHS/United States
GR  - P01AG025204/AG/NIA NIH HHS/United States
GR  - R01AG042210/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (amyloid beta-protein (1-42))
RN  - 0 (tau Proteins)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyloid beta-Peptides/*biosynthesis
MH  - Autophagy/physiology
MH  - Cognitive Dysfunction/*metabolism/pathology
MH  - Cohort Studies
MH  - Endosomes/*metabolism/pathology
MH  - Female
MH  - Hippocampus/*metabolism/pathology
MH  - Humans
MH  - Lysosomes/*metabolism/pathology
MH  - Male
MH  - Peptide Fragments/biosynthesis
MH  - tau Proteins/*biosynthesis
PMC - PMC4366294
MID - NIHMS658960
EDAT- 2015/03/11 06:00
MHDA- 2015/06/16 06:00
PMCR- 2016/04/01
CRDT- 2015/03/11 06:00
PHST- 2015/03/11 06:00 [entrez]
PHST- 2015/03/11 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1097/NEN.0000000000000179 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2015 Apr;74(4):345-58. doi: 
      10.1097/NEN.0000000000000179.