The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system

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Abstract

Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.

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Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease.

Yoshio Namba, Masanori Tomonaga, Hiroshi Kawasaki … (1991)

During the course of our immunohistochemical studies on the change of lipids in Alzheimer's disease brains by using antibody to apolipoprotein E, a protein having a special relevance to nervous tissue, we unexpectedly found that apo E immunoreactivity was associated with amyloid in both senile plaques and cerebral vessels and neurofibrillary tangles. The immunoreactivity was also found in amyloid of kuru plaques in Creutzfeldt-Jakob disease. Pretreatment of the sections with formic acid greatly enhanced immunoreactivity of senile and kuru plaques to antibody to apo E.

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Sequence identification of 2,375 human brain genes.

A Kerlavage, T Utterback, Mary Kelley … (1992)

We recently described a new approach for the rapid characterization of expressed genes by partial DNA sequencing to generate 'expressed sequence tags'. From a set of 600 human brain complementary DNA clones, 348 were informative nuclear-encoded messenger RNAs. We have now partially sequenced 2,672 new, independent cDNA clones isolated from four human brain cDNA libraries to generate 2,375 expressed sequence tags to nuclear-encoded genes. These sequences, together with 348 brain expressed sequence tags from our previous study, comprise more than 2,500 new human genes and 870,769 base pairs of DNA sequence. These data represent an approximate doubling of the number of human genes identified by DNA sequencing and may represent as many as 5% of the genes in the human genome.