1) Fusogenic properties

Ab could form ion channels or pores in the membrane, allowing calcium uptake and neurodegeneration. These effects are prevented by zinc (an AbetaP channel blocker) and by the removal of extracellular calcium, but are not prevented by antagonists of putative AbetaP cell surface receptors (Lin H, Bhatia R, Lal R (2001) Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology. Faseb J, 15, 2433-44.)

Anguiano M, ... , Lansbury PT. Protofibrillar Islet Amyloid Polypeptide Permeabilizes Synthetic Vesicles by a Pore-like Mechanism that May Be Relevant to Type II Diabetes., Biochemistry  2002 Sep;41(38):11338-43

2) Ab could mediate a chemotactic and activating effect on microglia and monocytes, via a G protein-coupled receptor (FPRL1)

3) Ab could increase the production of free radicals and boost oxidative stress
Butterfield DA, Amyloid beta-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain., Brain Pathol  2004 Oct;14(4):426-32 PubMed Abstract

4) Ab  could increase some metabolic pathways leading to apoptosis

5) Ab could activate vascular pathology:

The vascular actions of Abeta may contribute to the deleterious effects resulting from accumulation of this peptide in Alzheimer's dementia. Niwa, K et al. "Abeta-peptides enhance vasoconstriction in cerebral circulation." Am J Physiol Heart Circ Physiol. 281(6): H2417-H2424, 2001.

6) Ab could deregulate the complement immunological reaction: Ability of beta-amyloid fibrils to trigger activation of the classical C pathway and support for the hypothesis that C activation may be a component of the pathogenesis of Alzheimer's disease. Tacnet-Delorme et al. "beta-Amyloid Fibrils Activate the C1 Complex of Complement Under Physiological Conditions: Evidence for a Binding Site for Abeta on the C1q Globular Regions." J Immunol. 167(11): 6374-81, 2001.

See also: Moore KJ, ... , Freeman MW. A CD36-initiated signaling cascade mediates inflammatory effects of beta -amyloid., J Biol Chem  2002 Sep.

In the same way, there is an activation of microglial cells and astrocytes

7) Ab could modify the transport of cholesterol:

Yao ZX, Papadopoulos V. Function of b-amyloid in cholesterol transport: a lead to neurotoxicity., FASEB J  2002 Aug

8) Ab increases calcium influx trhough voltage-gated calcium channels

Elevated intracellular calcium could activate calpain that cleaves p35 to p25, to activate cdk5 that could phosporylate tau

9) Ab activates signalling patways: MAPK signalling

11) Neurotoxicity of intracellular Abeta deposits

12) Camacho IE. Peroxisome proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptide., J Neurosci  2004 Dec;24(48):10908-17

13) The levels of cholesterol could play a role in Abeta production:

- Abad-Rodriguez J. Neuronal membrane cholesterol loss enhances amyloid peptide generation., J Cell Biol  2004 Dec;167(5):953-60

- Kaether C. A lipid boundary separates APP and secretases and limits amyloid beta-peptide generation., J Cell Biol  2004 Dec;167(5):809-12

- see al Alzheimer and statins: