Differential distribution of laminins in Alzheimer disease and normal human brain tissue.

Immunocytochemistry, Western blotting, and RT-PCR were used to identify the isoforms of laminin expressed in the Alzheimer disease, but not in normal human brain tissue. We found that alpha 1 laminin was heavily over-expressed in Alzheimer disease frontal cortex, and localized in reactive astrocytes of the grey and white matter, and as punctate deposits in the senile placques of the Alzheimer brain tissue. Antibodies against the C-terminal neurite outgrowth domain of the gamma 1 laminin demonstrated expression of the gamma 1 laminin in GFAP-immunoreactive reactive astrocytes of the Alzheimer disease frontal cortex. The gamma 1 laminin was also heavily over-expressed in reactive astrocytes of both grey and white matter. Although antibodies against the C-terminal neurite outgrowth domain failed to localize gamma 1 laminin in senile plaques, antibodies against the N-terminal domains of the gamma 1 laminin demonstrated gamma 1 laminin as punctate deposits in the senile plaques. The present results indicate that enhanced and specialized expression patterns of alpha 1 and gamma 1 laminins distinctly associate these two laminins with the Alzheimer disease. The fact that domain specific antibodies localize both alpha1 and gamma 1 laminins in the senile plaques as punctate deposits and in astrocytes of both the gray and white matter indicate that these laminins and their specific domains may have distinct functions in the pathophysiology of the Alzheimer disease.