AF102B: A Novel M1 Agonist as a Rational Treatment Strategy in Alzheimer’s Disease

  • Abraham Fisher
  • Rachel Brandeis
  • Ishai Karton
  • Zipora Pittel
  • Shlomit Dachir
  • Michal Sapir
  • Y. Grunfeld
  • Aharon Levy
  • Eliahu Heldman
Part of the Advances in Behavioral Biology book series (ABBI, volume 36)


Alzheimer’s disease (AD), a progressive cerebral neurodegenerative disorder with no effective treatment as yet, is known to affect 5–7% of the population over age 65. This disorder is characterized by a progressive deterioration of cognitive and mnemonic abilities. Morphological, neurochemical and behavioral studies indicate a major degeneration of the central cholinergic.system in AD (1, 2). There is also evidence that noradrenergic, serotonergic, and somatostatin-like immunoreactivity are abnormal in AD, though to a lesser extent (for reviews see refs. 3 and 4). The contribution of the cholinergic dysfunction to the cognitive symptoms in AD is indicated by a direct correlation between loss of presynaptic cholinergic markers and mental test scores (1, 2). Postmortem evaluations of brains from patients with AD have revealed a select degeneration of cholinergic cells in the basal forebrain which project to the cerebral cortex and hippocampus (reviews 1–3). This degeneration is associated with a marked reduction of presynaptic cholinergic indices in these brain regions involved in cognitive processes (5). Somewhat conflicting results were reported regarding muscarinic receptors in AD. A loss of M2 muscarinic receptors was reported in a few studies (6–8 but see also 9, 10) while postsynaptic muscarinic receptors are relatively unchanged (6–9), decreased (10) or even upregulated (11).


Muscarinic Receptor Morris Water Maze Senile Dementia Muscarinic Agonist Passive Avoidance Task 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Abraham Fisher
    • 1
  • Rachel Brandeis
    • 1
  • Ishai Karton
    • 1
  • Zipora Pittel
    • 1
  • Shlomit Dachir
    • 1
  • Michal Sapir
    • 1
  • Y. Grunfeld
    • 1
  • Aharon Levy
    • 1
  • Eliahu Heldman
    • 1
  1. 1.Israel Institute for Biological ResearchNess-ZionaIsrael

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