title: Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain.
abstract: 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.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, 138-736, Republic of Korea.
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Eunsil
authors.initials: E
authors.lastname: Cho
authors.forename: Tae-Youn
authors.initials: TY
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Kim
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.forename: Jong S
authors.initials: JS
authors.lastname: Kim
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Koh
mesh_terms: 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*
chemical_list: 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