Interestingly, the proteins identified in the screen fall into three distinct categories. One set are proteins that are associated with Alzheimer's disease, including myelin basic protein, 14-3-3 protein, syntaxin binding protein munc18, transketolase, heat shock protein HSP70, reelin, and calcium/calmodulin kinase II (Table 1 ). Significant decrease in the amount of myelin basic protein has been reported in the white matter of Alzheimer's disease patients, accompanied by increased quantities of βamyloid peptides (21) . The presence of β-amyloid peptides containing senile plaques and neurofibrillary tangles are the two major pathological features in the brain of patients with Alzheimer's disease (22) . Interestingly, 14-3-3 proteins have also been demonstrated to be components of neurofibrillary tangles of Alzheimer's disease brains (23) . Syntaxin binding protein munc18 can powerfully regulate amyloid precursor protein metabolism and β-amyloid secretion through direct and indirect interactions with X11 proteins (24) . The activity of transketolase has been reported to be reduced in dementia of Alzheimer's type brain (25) . Heat shock protein HSP70 expression is significantly increased in the temporal cortex of patients with Alzheimer's disease (26) . Besides HSP70, other heat shock proteins are also linked with Alzheimer's disease. For example, increased synthesis of HSP27 has been suggested to play a role in preventing neuronal injury in AD (27) , and alpha-crystallin heat shock protein has a close relationship with neurofibrillary tangles of AD brains (28) . Reelin is a large secreted protein that controls cortical layering by signaling through the very low density lipoprotein receptor and apolipoprotein E receptor 2, thereby inducing tyrosine phosphorylation of the adaptor protein Disabled-1 (Dab1) and suppressing tau phosphorylation (29) . Neurofibrillary tangles comprised of highly phosphorylated tau proteins are a key component of Alzheimer's disease (30) . Enhanced activity of calcium/calmodulin kinase II has been suggested to contribute to phosphorylation of tau protein and lead to neurofibrillary tangle deposition and neuronal death in Alzheimer's disease (31) . Although the relationship between p62 and neurofibrillary tangles or neuritic plaques is unclear, both neurofibrillary tangles and dystrophic neuritis of neuritic plaques are associated with ubiquitin (32) , suggesting that dysfunction in ubiquitin-mediated proteolysis and the resulting accumulation of ubiquitinconjugated proteins may contribute to the origination of dystrophic neuritis and neurofibrillary tangles. Furthermore, p62 has been recently reported to accumulate early in neurofibrillary tangles in Alzheimer's disease (33) , suggesting that p62 may play an important role in Alzheimer's disease by interacting with those proteins through its UBA domain.