PMID- 23948903
OWN - NLM
STAT- MEDLINE
DCOM- 20140627
LR  - 20130925
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 37
IP  - 3
DP  - 2013
TI  - Animal models of the sporadic form of Alzheimer's disease: focus on the disease 
      and not just the lesions.
PG  - 469-74
LID - 10.3233/JAD-130827 [doi]
AB  - Alzheimer's disease is multifactorial and involves several different mechanisms. 
      The sporadic form of the disease accounts for over 99% of the cases. As of yet, 
      there is no practical and widely available animal model of the sporadic form of 
      the disease. In the Alzheimer's disease brain, the lysosomal enzyme asparaginyl 
      endopeptidase is activated and translocated from the neuronal lysosomes to the 
      cytoplasm, probably due to brain acidosis caused by ischemic changes associated 
      with age-associated microinfarcts. The activated asparaginyl endopeptidase 
      cleaves inhibitor-2 of protein phosphatase-2A, I2(PP2A), into I(2NTF) and I(2CTF) 
      which translocate to the neuronal cytoplasm and inhibit the protein phosphatase 
      activity and consequently the abnormal hyperphosphorylation of tau. Employing 
      adeno-associated virus serotype 1 (AAV1) vector containing I(2NTF-CTF) and 
      transduction of the brains of newborn rat pups with this virus, an animal model 
      has been generated. The AAV1-I(2NTF-CTF) rats show neurodegeneration and 
      cognitive impairment at 4 months and abnormal hyperphosphorylation and 
      aggregation of tau and intraneuronal accumulation of amyloid-beta at 13 months. The 
      AAV1-I(2NTF-CTF) rats not only offer a disease-relevant model of the sporadic 
      form of Alzheimer's disease but also represent a practical and widely available 
      animal model. This short perspective on the need to focus on and develop the 
      disease-relevant models of the sporadic form of Alzheimer's disease very much 
      reflects the thinking of Inge Grundke-Iqbal who passed away on September 22, 2012 
      and to whom this article is dedicated.
FAU - Iqbal, Khalid
AU  - Iqbal K
AD  - Department of Neurochemistry, New York State Institute for Basic Research in 
      Developmental Disabilities, Staten Island, NY, USA.
FAU - Bolognin, Silvia
AU  - Bolognin S
FAU - Wang, Xiaochuan
AU  - Wang X
FAU - Basurto-Islas, Gustavo
AU  - Basurto-Islas G
FAU - Blanchard, Julie
AU  - Blanchard J
FAU - Tung, Yunn Chyn
AU  - Tung YC
LA  - eng
GR  - AG019158/AG/NIA NIH HHS/United States
GR  - AG028538/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (tau Proteins)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Alzheimer Disease/genetics/*metabolism/*pathology
MH  - Animals
MH  - Brain/*metabolism/*pathology
MH  - *Disease Models, Animal
MH  - Humans
MH  - Protein Phosphatase 2/metabolism
MH  - Rats
MH  - tau Proteins/metabolism
EDAT- 2013/08/21 06:00
MHDA- 2014/06/28 06:00
CRDT- 2013/08/17 06:00
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/06/28 06:00 [medline]
AID - G662261G74H7G261 [pii]
AID - 10.3233/JAD-130827 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2013;37(3):469-74. doi: 10.3233/JAD-130827.