Summary. A transgenic mouse bearing mutant
transgenes linked to familial forms of Alzheimer’s
disease (AD) for the amyloid precursor protein and
presenilin-1 (TASTPM) showed Aß plaque deposition
and age-related histological changes in associated brain
pathology. The Aß present was of multiple forms,
including species with a C-terminus at position 40 or 42,
as well as an N-terminus at position 1 or truncated in a
pyro-3-glutamate form. Endogenous rodent Aß was also
present in the deposits. Laser capture microdissection
extracts showed that multimeric forms of Aß were
present in both plaque and tissue surrounding plaques.
Associated with the Aß deposits was evidence of an
inflammatory response characterised by the presence of
astrocytes. Also present in close association with the
deposits was phosphorylated tau and cathepsin D
immunolabelling. The incidence of astrocytes and of
phosphorylated tau and cathepsin D load showed that
both of these potential disease markers increased in
parallel to the age of the mice and with Aß deposition.
Immunohistochemical labelling of neurons in the cortex
and hippocampus of TASTPM mice suggested that the
areas of Aß deposition were associated with the loss of
neurons. TASTPM mice, therefore, exhibit a number of
the pathological characteristics of disease progression in
AD and may provide a means for assessment of novel
therapeutic agents directed towards modifying or halting
disease progression