Sporadic Alzheimer Disease and That Developing in Down’s Syndrome: The Immune System Attacking Self Rather Than Suppressing Infectious Disease Invaders, Toll Like Receptors Triggering Excessive Cytosolic Calcium, Excess Calcineurin Activation, Overexpress

Abstract

Alzheimer Disease may result from excessive stimulation of the innate immune system from development of underlying opportunistic infections and impaired age related selfrecognition as non-self, due to immunodeficiency and immunosenescence, resulting in excessive inflammation and runaway Beta-amyloid production (a component of the innate immune system) causing cytosolic calcium overload. Excessive cytosolic calcium may cause over activation of calcineurin and inactivation of cis-trans prolyl isomerase (Pin1), with subsequent loss of dendritic spine maintenance, and synaptic destruction. Improving immune function, identifying and treating infections, avoiding runaway Betaamyloid production, inhibiting calcineurin in a manner similar to that utilized in preventing tissue transplant rejection, maintaining the negative feedback loop between regulators of calcineurin1 (RCAN1) and calcineurin, may lead to improved prevention and treatment of Alzheimer Disease and Down's syndrome.