Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer's disease

Abstract

Integrins belonging to different subfamilies can be identified immunohistochemically in cerebral amyloid plaques. Monoclonal antibodies against the VLA family beta 1-integrins show staining of the corona of classical amyloid plaques for beta 1, alpha 3 and alpha 6. Immunostaining reveal also the presence of collagen and laminin in the corona. Activated microglial cells in classical plaques strongly express receptors belonging to the LeuCAM family (beta 2 integrins). The ligands ICAM and activated complement C3 are found in both amorphous and classical plaques. Vitronectin receptor (alpha v) is found in glial cells in classical plaques but its ligand vitronectin is seen in both amorphous and classical plaques. The data presented here demonstrate the presence of different cellular and substrate adhesive molecules (integrins) and their ligands in classical plaques. The findings suggest that amyloid plaques show signs of regeneration and tissue remodelling.

Whole genome association scan for genetic polymorphisms influencing information processing speed

“…Type 4 collagen (COL4A1 is part of the gene family coding for this protein) has also been localised within the senile plaques as punctuate deposits (Kiuchi et al, 2002); and integrins (e.g., ITGA2 gene product) have been identified immunohistochemically in cerebal amyloid plaques (Eikelenboom et al, 1994), again suggesting that variation in these relevant genes might be important. By the same logic, reduced levels of protein kinase C alpha (e.g., PRKCA gene product) have been linked to an altered amyloid precursor protein secretion in fibroblasts from AD patients (Benussi et al, 1998).…”

“…Of the significant genes we identified in this pathway, several are particularly interesting due to their link with AD. The alpha 1 laminin isoform is over-expressed in AD frontal cortex and presents as punctate deposits in the senile plaques, and in the astrocytes of grey and white matter (Palu and Liesi, 2002), providing a basis for linking LAMA1 to the aetiology of AD.Type 4 collagen (COL4A1 is part of the gene family coding for this protein) has also been localised within the senile plaques as punctuate deposits (Kiuchi et al, 2002); and integrins (e.g., ITGA2 gene product) have been identified immunohistochemically in cerebal amyloid plaques (Eikelenboom et al, 1994), again suggesting that variation in these relevant genes might be important. By the same logic, reduced levels of protein kinase C alpha (e.g., PRKCA gene product) have been linked to an altered amyloid precursor protein secretion in fibroblasts from AD patients (Benussi et al, 1998).…”

Cell Surface Amyloid β-Protein Precursor Colocalizes with β1 Integrins at Substrate Contact Sites in Neural Cells

“…A␤ is, of course, the principal constituent of senile plaques, and, in "classical" plaques, ␤PP-containing dystrophic neurites are found within and around these deposits. Interestingly, various integrin receptors and their ligands also have been detected within senile plaques by immunocytochemistry (Eikelenboom et al, 1994). It is possible that these molecules participate in the cascade of events that result in amyloidogenesis in brain and in the subsequent formation of the senile plaque.…”

How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes

“…In recent years it has become obvious that microglial cells can be activated by factors such as brain trauma, ischaemia or neurodegeneration. Activated microglia express markers, such as MHC class I and class II molecules, together with integrins and Fc receptors (Eikelenboom et al ., 1994;. In the AD brain, activation of microglia by A β is associated with chemotactic responses to it, consistent with the extensive clustering of activated microglia at sites of A β deposition ( Terry & Wisniewski, 1975).…”