The relationship between senile plaques and cerebral blood vessels in Alzheimer’s disease and senile dementia

Miyakawa, Taihei; Shimoji, Akitomo; Kuramoto, Ryoko; Higuchi, Yasushi

doi:10.1007/bf02932857

Cited by 199 publications

(86 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The detection of APP mRNA in these cells strengthens the possibility that at least one form of amyloid 83-protein-cerebrovascular-could originate locally from blood vessels (24,25).…”

mentioning

confidence: 58%

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

Goldgaber

Harris

Hla

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

510

237

View full text Add to dashboard Cite

We have analyzed the modulation of amyloid (3-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.The amyloid A3-protein precursor (APP) gene codes for a family of proteins, each containing a 42-amino acid fragment called amyloid 3 or A4 protein, that is found in brains and the cerebrovasculature of Alzheimer disease, Down syndrome, hereditary cerebral hemorrhage (Dutch type), and aging (1)(2)(3)(4)(5). The APP gene is transcriptionally active in a variety of tissues, highly conserved in evolution, maps to human chromosome 21 (6-10), and probably has no mutations associated with Alzheimer disease (11, 12). Transcripts containing three similar but nonidentical open reading frames have been identified (13)(14)(15)(16)(17). In situ hybridization studies show a very complex pattern of the APP gene expression in brain (18-23).Different levels of APP mRNAs were detected in neurons, some glial cells, and cells that compose blood vessels, presumably some endothelial cells (23). The detection of APP mRNA in these cells strengthens the possibility that at least one form of amyloid 83-protein-cerebrovascular-could originate locally from blood vessels (24, 25).The importance ofunderstanding the regulation ofthe APP gene is underscored by two observations. First, there are differences between Alzheimer disease patients and controls in the levels of APP mRNAs in certain brain regions (19,23,(26)(27)(28)(29)(30). Second, the difference in the level of APP mRNAs between trisomy 21 Down-syndrome patients and controls having two chromosomes 21 was higher than the expected 3:2 ratio (9). In the absence of structural mutations, aberrant levels of the precursor protein may contribute to pathology. These observations suggest that there is aberrant regulation...

show abstract

“…The detection of APP mRNA in these cells strengthens the possibility that at least one form of amyloid 83-protein-cerebrovascular-could originate locally from blood vessels (24,25).…”

mentioning

confidence: 58%

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

Goldgaber

Harris

Hla

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

510

237

View full text Add to dashboard Cite

show abstract

“…Contrary to the popularized dogma that all amyloid plaques arise from extracellular deposition, plaques may originate from vessels [44], neurons [11][12][13][14][15][16][17], Purkinje cell dendritic processes [67] and astrocytes [46]. In one example, recent attention has turned towards pathological events within the neuron suggesting that cell death could come Fig.…”

Section: Unique Mechanisms Of Plaque Formationmentioning

confidence: 99%

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

D’Andrea

Cole

Ard

2004

Neurobiology of Aging

198

131

View full text Add to dashboard Cite

Alzheimer disease (AD) involves glial inflammation associated with amyloid plaques. The role of the microglial cells in the AD brain is controversial, as it remains unclear if the microglia form the amyloid fibrils of plaques or react to them in a macrophage-phagocytic role. Also, it is not known why microglia are preferentially associated with some amyloid plaque types. This review will provide substantial evidence to support the phagocytic role of microglia in the brain as well as explain why microglia are generally associated with specific plaque types that may be explained through their unique mechanisms of formation. In summary, the data presented suggests that plaque associated microglial activation is typically subsequent to specific amyloid plaque formations in the AD brain.

show abstract

“…The fragment could also be localized to vascular basement membranes, which are abundant in our preparations. ABP fibrils have been localized to capillary and arteriolar basement membranes in AD cortex (28)(29)(30). Amyloid fibrils in certain systemic amyloidoses are characteristically localized to vascular basement membranes (31), suggesting that proteases that process amyloidogenic precursors or macromolecules that promote fibrillogenesis are enriched in this structure.…”

Section: Morphology and Yield Of Cerebral Microvessel Fractionsmentioning

confidence: 99%

Identification of a stable fragment of the Alzheimer amyloid precursor containing the beta-protein in brain microvessels.

Tamaoka

Kalaria

Lieberburg

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

119

View full text Add to dashboard Cite

Altered proteolysis of the (3-amyloid precursor protein (PAPP) (36 and 38 yr), and 18 non-AD subjects (fetal-78 yr). Frozen nonneural tissues (renal cortex, heart, spleen, and adrenal) and fresh or frozen animal brains (rat, guinea pig, rabbit, and cow) were also used to prepare microvessels. Microvessels were purified at 40C by a modification of the method of Tsuji et al. (9). Cerebral gray matter (usually 5-10 g of wet weight) was minced into -2 mm3 blocks, suspended in 5-10 vol of Tris-buffered saline (TBS) (50 mM Tris/150 mM sodium chloride/2 mM EDTA/0.1 mM diisopropyl fluorophosphate/ leupeptin at 1 Ag/ml/pepstatin at 0.1 ug/ml/7-amino-1-chloro-3-tosylamide-2-heptanone at 1 tig/ml, pH 7.6), and homogenized with a motor-driven, loosely fitting Teflon pestle (5-10 up-and-down strokes). The homogenate was sieved through 73-,.m nylon mesh. The flow-through fraction was saved as the nonvascular brain fraction, and the mesh was washed in TBS buffer to resuspend the retained material.This suspension was placed on a column of 425-to 600-Iumdiameter glass beads (Sigma) with a sheet of 73-,um nylon mesh at the bottom. The column was washed with 5-10 vol of TBS, and its contents were placed in a beaker of 50-100 ml of TBS. Microvessels were separated from the glass beads by agitation with a metal rod. The beads settled, and the microvessel suspension was decanted and centrifuged at 10,000 x g for 30 min. The resultant pellet was resuspended in 0.25 M sucrose, homogenized (five strokes), and layered on a discontinuous sucrose-density gradient (8 ml each of 1.0 M, 1.3 M, and 1.5 M sucrose in H20). After centrifugation at 58,000 x g in an SW 28 rotor for 120 min, the microvessel fraction was recovered as a pellet from the bottom of the tube and resuspended in 1-2 ml of TBS. Some microvessel fractions were prepared from fresh brain tissue by an alternate but comparable purification method described by Kalaria and Harik (10).To separate large from small microvessels, the suspension retained on the 73-pum mesh was sieved through a 153-,um nylon mesh, and the latter was washed in TBS to resuspend the retained material. This suspension was centrifuged at 10,000 x g for 30 min at 40C, and the resultant pellet was layered on a sucrose gradient as described above. For purification of small microvessels, the flow-through fraction off the 153-,um mesh was successively processed over the glass bead column and the sucrose gradient as described above.Purified microvessel fractions were homogenized (10 strokes) in a Teflon homogenizer, mixed 3:1 with 4x SDS Abbreviations: 8APP, 13-amyloid precursor protein; FL-f3APP, fulllength fAPP; A,8P, amyloid ,1-protein; AD, Alzheimer disease. 1345The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

The relationship between senile plaques and cerebral blood vessels in Alzheimer’s disease and senile dementia

Cited by 199 publications

References 15 publications

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

Identification of a stable fragment of the Alzheimer amyloid precursor containing the beta-protein in brain microvessels.

Contact Info

Product

Resources

About