scholarly journals Synaptophysin and Synaptojanin-1 in Down Syndrome are Differentially Affected by Alzheimer's Disease

2014 ◽  
Vol 42 (3) ◽  
pp. 767-775 ◽  
Author(s):  
Sarah B. Martin ◽  
Amy L.S. Dowling ◽  
Joann Lianekhammy ◽  
Ira T. Lott ◽  
Eric Doran ◽  
...  
2015 ◽  
Vol 112 (38) ◽  
pp. 11965-11970 ◽  
Author(s):  
Li Zhu ◽  
Minghao Zhong ◽  
Gregory A. Elder ◽  
Mary Sano ◽  
David M. Holtzman ◽  
...  

The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer’s disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.


Amino Acids ◽  
2001 ◽  
Vol 21 (3) ◽  
pp. 293-301 ◽  
Author(s):  
M. Bajo ◽  
B. C. Yoo ◽  
N. Cairns ◽  
M. Gratzer ◽  
G. Lubec

2015 ◽  
Vol 21 (5) ◽  
pp. 707-716 ◽  
Author(s):  
S Kim ◽  
Y Sato ◽  
P S Mohan ◽  
C Peterhoff ◽  
A Pensalfini ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document