PMID- 24991237
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140703
LR  - 20211021
IS  - 1758-9193 (Print)
IS  - 1758-9193 (Electronic)
VI  - 6
IP  - 3
DP  - 2014
TI  - beta-amyloid deposition is shifted to the vasculature and memory impairment is 
      exacerbated when hyperhomocysteinemia is induced in APP/PS1 transgenic mice.
PG  - 32
LID - 10.1186/alzrt262 [doi]
AB  - INTRODUCTION: Vascular dementia is the second most common cause of dementia after 
      Alzheimer's disease (AD). In addition, it is estimated that almost half of all AD 
      patients have significant cerebrovascular disease comorbid with their AD 
      pathology. We hypothesized that cerebrovascular disease significantly impacts AD 
      pathological progression. METHODS: We used a dietary model of cerebrovascular 
      disease that relies on the induction of hyperhomocysteinemia (HHcy). HHcy is a 
      significant clinical risk factor for stroke, cardiovascular disease and type 2 
      diabetes. In the present study, we induced HHcy in APP/PS1 transgenic mice. 
      RESULTS: While total beta-amyloid (Abeta) load is unchanged across groups, Congophilic 
      amyloid deposition was decreased in the parenchyma and significantly increased in 
      the vasculature as cerebral amyloid angiopathy (CAA; vascular amyloid deposition) 
      in HHcy APP/PS1 mice. We also found that HHcy induced more microhemorrhages in 
      the APP/PS1 mice than in the wild-type mice and that it switched the 
      neuroinflammatory phenotype from an M2a biased state to an M1 biased state. 
      Associated with these changes was an induction of the matrix metalloproteinase 
      protein 2 (MMP2) and MMP9 systems. Interestingly, after 6 months of HHcy, the 
      APP/PS1 mice were cognitively worse than wild-type HHcy mice or APP/PS1 mice, 
      indicative of an additive effect of the cerebrovascular pathology and amyloid 
      deposition. CONCLUSIONS: These data show that cerebrovascular disease can 
      significantly impact Abeta distribution in the brain, favoring vascular deposition. 
      We predict that the presence of cerebrovascular disease with AD will have a 
      significant impact on AD progression and the efficacy of therapeutics.
FAU - Sudduth, Tiffany L
AU  - Sudduth TL
AD  - Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, 
      800 S. Limestone St., Lexington, KY 40536, USA.
FAU - Weekman, Erica M
AU  - Weekman EM
AD  - Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, 
      800 S. Limestone St., Lexington, KY 40536, USA.
FAU - Brothers, Holly M
AU  - Brothers HM
AD  - Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, 
      800 S. Limestone St., Lexington, KY 40536, USA.
FAU - Braun, Kaitlyn
AU  - Braun K
AD  - Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, 
      800 S. Limestone St., Lexington, KY 40536, USA.
FAU - Wilcock, Donna M
AU  - Wilcock DM
AD  - Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, 
      800 S. Limestone St., Lexington, KY 40536, USA.
LA  - eng
GR  - R01 NS079637/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20140609
PL  - England
TA  - Alzheimers Res Ther
JT  - Alzheimer's research & therapy
JID - 101511643
PMC - PMC4078260
EDAT- 2014/07/06 06:00
MHDA- 2014/07/06 06:01
PMCR- 2014/06/09
CRDT- 2014/07/04 06:00
PHST- 2014/01/16 00:00 [received]
PHST- 2014/05/21 00:00 [accepted]
PHST- 2014/07/04 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/07/06 06:01 [medline]
PHST- 2014/06/09 00:00 [pmc-release]
AID - alzrt262 [pii]
AID - 10.1186/alzrt262 [doi]
PST - epublish
SO  - Alzheimers Res Ther. 2014 Jun 9;6(3):32. doi: 10.1186/alzrt262. eCollection 2014.