PMID- 26402627
OWN - NLM
STAT- MEDLINE
DCOM- 20160630
LR  - 20150925
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 46
IP  - 4
DP  - 2015
TI  - Brain Amyloidosis and BDNF Deficiency Have Opposite Effects on Brain Volumes in 
      AbetaPP/PS1 Mice Both in vivo and ex vivo.
PG  - 929-46
LID - 10.3233/JAD-150059 [doi]
AB  - Magnetic resonance imaging (MRI) volumetry is widely used in Alzheimer's disease 
      (AD) research and diagnostics alongside clinical assessment. Yet few MRI 
      volumetry studies have been conducted in AD model mice with mixed results. We 
      performed in vivo and ex vivo MRI and extensive postmortem histological analysis 
      in transgenic mice derived from crossing amyloid plaque producing AbetaPP/PS1 mice 
      with brain-derived neurotrophic factor (BDNF) +/- mice. This allowed us to 
      compare developmental volumetric changes due to BDNF deficiency with progressive 
      changes due to amyloid accumulation. We found decreased whole brain volume at 3 
      months and decreased cortical volume at both 3 and 8 months in vivo in BDNF +/- 
      Tg mice but increased whole brain and cortical volumes at 8 months in AbetaPP/PS1 
      mice. Consistent with this, the postmortem histological analysis showed decreased 
      brain parenchymal area in BDNF +/- mice but an increase in AbetaPP/PS1 mice. BDNF 
      gene deficiency did not affect brain amyloid load or astrogliosis, but led to 
      decreased dentate gyrus length, whereas AbetaPP/PS1 mice had significantly increased 
      amyloid load, astrogliosis, and decreased neurogenesis. Distinct and 
      layer-specific effects were found in the hippocampus of AbetaPP/PS1 and BDNF +/- 
      mice. In contrast to human AD patients, brain atrophy in amyloid producing mice 
      appears to be masked by volume increase due to amyloid accumulation and 
      especially accompanying astrogliosis. Our results indicate that cortical MRI 
      volumetry can be used to some extent as a proxy to progressive brain amyloidosis 
      in preclinical studies.
FAU - Karkkainen, Elisa
AU  - Karkkainen E
AD  - A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
FAU - Lahtinen, Hanna-Maija
AU  - Lahtinen HM
AD  - A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
FAU - Narvainen, Johanna
AU  - Narvainen J
AD  - A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
FAU - Grohn, Olli
AU  - Grohn O
AD  - A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
FAU - Tanila, Heikki
AU  - Tanila H
AD  - A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
AD  - Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Presenilin-1)
SB  - IM
MH  - Age Factors
MH  - Alzheimer Disease/*pathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Amyloidosis/*metabolism/pathology
MH  - Analysis of Variance
MH  - Animals
MH  - Brain/*metabolism/*pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation/genetics
MH  - Presenilin-1/genetics
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - BDNF
OT  - amyloid plaques
OT  - amyloid-beta protein precursor
OT  - magnetic resonance imaging
OT  - presenilin -1
OT  - volumetry
EDAT- 2015/09/25 06:00
MHDA- 2016/07/01 06:00
CRDT- 2015/09/25 06:00
PHST- 2015/09/25 06:00 [entrez]
PHST- 2015/09/25 06:00 [pubmed]
PHST- 2016/07/01 06:00 [medline]
AID - JAD150059 [pii]
AID - 10.3233/JAD-150059 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2015;46(4):929-46. doi: 10.3233/JAD-150059.