Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain.
Both apolipoprotein E (apoE) and zinc are involved in amyloid β (Aβ) aggregation and deposition, in the hallmark neuropathology of Alzheimer's disease (AD). Recent studies have suggested that interaction of apoE with metal ions may accelerate amyloidogenesis in the brain. Here we examined the impact of apoE deficiency on the histochemically reactive zinc pool in the brains of apoE knockout mice. While there was no change in total contents of metals (zinc, copper, and iron), the level of histochemically reactive zinc (principally synaptic zinc) was significantly reduced in the apoE-deficient brain compared to wild-type. This reduction was accompanied by reduced expressions of the presynaptic zinc transporter, ZnT3, as well as of the δ-subunit of the adaptor protein complex-3 (AP3δ), which is responsible for post-translational stability and activity of ZnT3. In addition, the level of histochemically reactive zinc was also decreased in the cerebrovascular micro-vessels of apoE-deficient mice, the site of cerebral amyloid angiopathy in AD. These results suggest that apoE may affect the cerebral free zinc pool that contributes to AD pathology.
Lee
Joo-Yong
JY
Asan Institute for Life Sciences, Asan Medical Center, Seoul, 138-736, Republic of Korea.
Cho
Eunsil
E
Kim
Tae-Youn
TY
Kim
Dong-Kyu
DK
Palmiter
Richard D
RD
Volitakis
Irene
I
Kim
Jong S
JS
Bush
Ashley I
AI
Koh
Jae-Young
JY
D033963:Adaptor Protein Complex 3 / Q000096:biosynthesis; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits / Q000096:biosynthesis; D013572:Synaptic Vesicles / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D033963:Adaptor Protein Complex 3; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D021122:Protein Subunits; C491177:Slc30a3 protein, mouse; D003300:Copper; D007501:Iron; D015032:Zinc