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Pathological Mechanisms in Alzheimer's Disease

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Compartment	Cell/Neuron	Receptor	Channel	Extracellular Pathological Agent (PA)	Intracellular Pathological Agent (PA)	PA Action	Drug	Drug Action	Stage	Note	Detail
General or unspecified	CA1 pyramidal neuron		I A	β-Amyloid		Inhibits			Early	View	Show
	CA1 pyramidal neuron		I Calcium	β-Amyloid		Increases	Nifedipine	Blocks		View	Show
	CA1 pyramidal neuron			β-Amyloid		Inhibits			Early	View	Show
Dendrite	CA1 pyramidal neuron		I A	β-Amyloid		Inhibits			Early	View	Show
	CA1 pyramidal neuron	NMDA	I Calcium	β-Amyloid		Inhibits				View	Show
	Olfactory bulb mitral cell	GabaA		Aluminum		Potentiates			Early	View	Show
	CA1 pyramidal neuron	Glutamate		β-Amyloid		Inhibits			Early	View	Show
				β-Amyloid		Inhibits			Early	View	Show
	Cerebellar purkinje cell			β-Amyloid		Induces			Early	View	Show
	Brain slice preparations			Amyloid plaques		Increases				View	Show
	Golgi impregnation - Animal post-mortem brains			β-Amyloid		Reduces			Early	View	Show
Apical dendrite	Neocortical pyramidal neuron: deep			β-Amyloid		Reduces			Early	View	Show
Apical dendrite	CA1 pyramidal neuron		I Sodium		protein kinase C	Inhibits			Early	View	Show
Distal apical dendrite	Golgi impregnation - Animal post-mortem brains / Neocortical pyramidal neuron: deep			Nerve Growth Factor (NGF)		Increases				View	Show
Soma	CA1 pyramidal neuron		I A	β-Amyloid		Inhibits			Early	View	Show
Soma	Olfactory bulb mitral cell	GabaA		Aluminum		Potentiates			Early	View	Show
		AMPA		β-Amyloid		Inhibits			Early	View	Show
			I L high threshold	β-Amyloid		Reduces	Verapamil	Blocks	Early	View	Show
			I Potassium	β-Amyloid		Modulates			Early	View	Show
	Oocyte	Nicotinic Cholinergic Receptors		β-Amyloid		Inhibits			Early	View	Show
				β-Amyloid		Is neurotoxic			Early	View	Show
	SH-SY-5Y human neuroblastoma cells		I L high threshold		MAP Kinase	Induces	Okadaic Acid	Increases		View	Show
			I L high threshold	Beta-amyloid (1-42)	Tau protein	Increases	Calpain Inhibitor I P35 Antisense Oligonucleotides Verapamil	Blocks		View	Show
	Cultured cortical neurons		I L high threshold		Presenilin-1	Reduces				View	Show
				β-Amyloid		Inhibits			Early	View	Show
	Isolated neurons of the land snake Helix		I K				Donepezil	Modulates		View	Show
				Beta amyloid plaques		Inhibits				View	Show
	Cultured cortical neurons			Protofibrillar Abeta		Increases				View	Show
	Cerebellar granule cell		I A	β-Amyloid (1-40)		Increases	brefeldin A cycloheximide	Blocks		View	Show
				β-Amyloid		Inhibits			Early	View	Show
				β-Amyloid		Inhibits			Early	View	Show
	CA1 pyramidal neuron	Nicotinic		β-Amyloid		Inhibits			Early	View	Show
	Brain slice preparations			β-Amyloid		Inhibits	Nicotine	Reverses	Early	View	Show
				BDNF (Brain-derived neurotrophic factor)	Cytoskeleton-associated protein (Arc)	Is Required For			Early	View	Show
	Brain slice preparations	Nicotinic		Nicotine		Potentiates			Late	View	Show
					Neurofibrillary tangles (NFT)	Is Correlated with			Late	View	Show
	Human Post-mortem Study				Drebrin	Is Correlated with			Early	View	Show
	Brain slice preparations / CA1 pyramidal neuron			β-Amyloid		Reduces	Rolipram	Blocks	Early	View	Show
	Human Post-mortem Study / Dentate granule cell				Apolipoprotein E4 (Apo E4)	Is Inversely Correlated with			Early	View	Show
				Beta-amyloid (1-42)		Increases	alpha7 nicotinic receptor antagonists	Blocks		View	Show
	Brain slice preparations	Muscarinic	I L high threshold	β-Amyloid		Reduces	Atropine Calcicludine Pirenzepine	Blocks		View	Show
	Brain slice preparations	Nicotinic		Galantamine		Reduces	Mecamylamine Sulpiride	Opposes	Late	View	Show
				Nicotine		Reduces			Late	View	Show
	Brain slice preparations	Cholinergic Receptors Nicotinic		β-Amyloid		Antagonizes	Acetyl Choline Choline Nicotine	Opposes	Early	View	Show
	Brain slice preparations	Cholinergic Receptors Nicotinic		Dihydro-beta-erythroidine (DHbetaE)		Induces	Clozapine	Reverses	Early	View	Show
		Glutamate		β-Amyloid		Reduces	alpha7 nicotinic receptor antagonists NMDA receptor blockers	Blocks	Early	View	Show
				β-Amyloid		Inhibits	Nicotine	Protects		View	Show
	Golgi impregnation - Animal post-mortem brains			Oral docosahexanoic acid (DHA)		Increases	Choline Uridine	Increases		View	Show
	Brain slice preparations		I Sodium	β-Amyloid					Early	View	Show
	Behavioral study	Adrenergic Beta		β-Amyloid			CL316243	Reverses	Early	View	Show
	Human Post-mortem Study			β-Amyloid		Induces			Early	View	Show
		NMDA		Abeta-derived diffusible ligands (ADDLs)		Induces			Early	View	Show
	Brain slice preparations			β-Amyloid	TNFalpha	Inhibits			Early	View	Show
	Brain slice preparations / CA3 pyramidal neuron				BACE1 (beta-secretase)	Is Required For	Calcium (extracellular)	Reverses	Early	View	Show
				β-Amyloid		Induces	Histidine-associating Compounds	Blocks	Early	View	Show

This database was supported by the Human Brain Project (NIDCD, NIMH, NIA, NICD, NINDS) and MURI (Multidisciplinary University Research Initiative). It is now supported by RO1 DC 009977 from the National Institute for Deafness and other Communication Disorders.
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