| Alzheimer's disease (AD) is a devastating illness that affects many elderly individuals. The current prevailing hypotheses for AD pathogenesis: the "amyloid" cascade hypothesis and the cholinergic hypothesis of memory impairment, dominate current approaches towards developing therapeutic strategies for preventing disease progression. Using a preclinical transgenic animal model which over expresses a mutation associated with a familial form of AD, the potential interaction between the beta-amyloid protein, a ∼4 kDa protein that deposits in the brains of patients, and the choline transporter, a newly identified selective transporter for choline in brain, are explored. A selective interaction between the choline transporter and the more pathogenic species of beta-amyloid that is 42 amino acids in length was observed. Although the cholinergic neurotransmitter system in AD is neither the only nor the first neurotransmitter system affected, the direct "cholinotoxic" effects of beta-amyloid acting via the choline transporter may contribute to disease progression. |
