Title

Degeneration of β-amyloid-associated cholinergic structures in transgenic APPSW mice

Document Type

Article

Department

Brain and Mind Institute

Abstract

Cholinergic dysfunction is a consistent feature of Alzheimer’s disease, and the interrelationship between β-amyloid deposits, inflammation and early cholinergic cell loss is still not fully understood. To characterize the mechanisms by which β-amyloid and pro-inflammatory cytokines may exert specific degenerating actions on cholinergic cells ultrastructural investigations by electron microscopy were performed in brain sections from transgenic Tg2576 mice that express the Swedish double mutation of the human amyloid precursor protein and progressively develop β-amyloid plaques during aging. Both light and electron microscopical investigations of the cerebral cortex of 19-month-old transgenic mice revealed a number of pathological tissue responses in close proximity of β-amyloid plaques, such as activated microglia, astroglial proliferation, increased number of fibrous astrocytes, brain edema, degeneration of nerve cells, dendrites and axon terminals. Ultrastructural detection of choline acetyl transferase (ChAT)-immunostaining in cerebral cortical sections of transgenic mice clearly demonstrated degeneration of ChAT-immunoreactive fibres in the environment of β-amyloid plaques and activated glial cells suggesting a role of β-amyloid and/or inflammation in specific degeneration of cholinergic synaptic structures.

Comments

This work was published before the author joined Aga Khan University.

Publication

Brain Research

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