Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact.

Abstract

The cloned cDNA encoding the rat cognate of the human A4 amyloid precursor protein was isolated from a rat brain library. The predicted primary structure of the 695‐amino acid‐long protein displays 97% identity to its human homologue shown previously to resemble an integral membrane protein. The protein was detected in rodent brain and muscle by Western blot analysis. Using in situ hybridization and immunocytochemistry on rat brain sections, we discovered that rat amyloidogenic glycoprotein (rAG) and its mRNA are ubiquitously and abundantly expressed in neurons indicating a neuronal original for the amyloid deposits observed in humans with Alzheimer's disease (AD). The protein appears in patches on or near the plasma membranes of neurons suggesting a role for this protein in cell contact. Highest expression was seen in rat brain regions where amyloid is deposited in AD but also in areas which do not contain deposits in AD. Since amyloid deposits are rarely observed in rat brain, we conclude that high expression of AG is not the sole cause of amyloidosis.

Differential APP gene expression in rat cerebral cortex, meninges, and primary astroglial, microglial and neuronal cultures

“…The highest level of APP mRNA was found in the meninges. High levels ofAPP mRNA were detected in neurons in agreement with most in situ hybridization studies [17][18][19][20][21][22][23][24]. Microglia and astrocytes contained an equivalent amount of APP mRNA which was lower than that of neurons, The higher steady-state level of APP mRNA in neurons compared to glial cells indicates ccll-specific transcriptional regulation of APP gene expression which may be relevant to the functional role of APP in these different cell types.…”

“…If over-expression of APP leads to flAP deposition, it is imperative to characterize APP gene expression in individual cell types of the CNS. High levels of APP mRNA and protein detected by in situ hybridization and immunocytochemistry suggest that flAP in the parenchymal amyloid deposits originates in neurons [17][18][19][20][21][22][23][24]. The close association of micro.…”

“…The rat cerebral cortex was used as it conveniently provides a sufficient number of cells to pursue these experiments. Regulation of APP gene expression in the rat is likely to be closely related to that of the human since there is 97% homology in their cDNAs [17]. In addition, the human APP promoter is active in rat PCI2 cells [41] and shows neuron specific expression in a transgenic mouse [42].…”

Human and rodent Alzheimer β‐amyloid peptides acquire distinct conformations in membrane‐mimicking solvents

“…Similar deposits have been detected in aged monkeys, dogs, and polar bears, but rarely have they been found in rats and mice (Selkoe, 1989). The sequences of P-amyloid precursor proteins of mice (Yamada et al, 1987) and rats (Shivers et al, 1988), deduced from cDNA clones, are about 90% similar to the human P-amyloid precursor protein. Three amino acid substitutions are found in the A4 region of rodents.…”

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

“…Likewise, ectodermal syntaxin 13, highly enriched in the brain (Advanti et al, 1998), and brain-specific aldolase C (Mukai et al, 1991) are expressed by MSCs. NMDA glutamate binding protein (Kumar et al, 1991) and APP (Shivers et al, 1988) represent additional neural genes transcribed by MSCs. These observations are consistent with our previous finding that the MSCs express low levels of NSE (Woodbury et al, 2000).…”