Table 1.

Association of ApoE to pre-symptomatic risk, prognosis, and response to treatment.

	Phenotype	Risk	Prognosis	Treatment
HYPERLIPIDEMIA (Mahley, 1988; Mahley et al., 1999; Maitland-Van Der Zee et al., 2003; Nieminen et al., 2008; Dergunov, 2011)
Familial hyperlipidemia and hypercholesterolemia	E2	(−)		Highest response to lipid-lowering therapy
	E4	+		Lowest response to lipid-lowering therapy
				Lowest compliance to treatment
				Highest response to low fat diet
Familial dysbetalipoproteinemia	E2	+
	E4
CARDIOVASCULAR DISEASES (Lahoz et al., 2001; Eichner et al., 2002; Masson et al., 2003; Song et al., 2004; Martinez-Gonzalez and Sudlow, 2006; Stehle et al., 2008; Mahley et al., 2009; Guo et al., 2011; Khan et al., 2013; Rannikmae et al., 2013)
Stroke	E2
	E4	(+)	Worst prognosis
			↑ Risk of death*
Coronary heart disease	E2	(−)
	E4	+	↑ Risk of death
Cerebral amyloid angiopathy (CAA)	E2		↑ Risk hemorrhage
	E4	+	↑ Risk hemorrhage
			↑ Severity
			↑ Risk death
NEURODEGENERATIVE DISEASES (Poirier et al., 1993; De La Fuente-Fernandez et al., 1999; Bedlack et al., 2000; Leduc et al., 2011; Verghese et al., 2011; Panza et al., 2012; Yin et al., 2012)
Alzheimer disease (AD)	E2	−	Later onset
	E4	+	Earlier onset	Cognition: Lowest response or no improvement in persons with dementia but higher response in persons with mild cognitive impairment Biomarkers (amyloid and CSF tau): higher response in persons with dementia
			↑ Neuropsychiatric symptoms
Vascular disease-associated cognitive impairment	E2
	E4		↑ Risk dementia
Lewy body disease	E2
	E4	(+)	↑ Risk dementia
Pick's disease	E2
	E4		Earlier onset
			↑ Risk dementia
Corticobasal degeneration	E2
	E4		↑ Risk dementia
Down'syndrome	E2
	E4		Faster progression
			↑ Risk dementia
Parkinson's disease (PD)	E2	+
			↑ Risk dementia	E4/4: ↑ Drug-induced hallucination
Amyotrophic lateral sclerosis (ALS)	E2		Later onset
	E4		Earlier onset
			Worst prognosis
Age-related macular degeneration	E2	(+)	Earlier onset
	E4	(−)	Later onset
AUTOIMMUNE DISEASES (Corder et al., 1998; Roselaar and Daugherty, 1998; De Bont et al., 1999; Mahley et al., 2009; Vitek et al., 2009; Kuhlmann et al., 2010; Zhang et al., 2011)
Human immunodeficiency virus (HIV)	E2			(↑ Risk hypertriglyceridemia)
	E4	(+)	↑ Risk dementia	(↑ Risk hypertriglyceridemia)
			↑ Risk Peripheral neuropathy
			↑ Risk AIDS
Acquired immunodeficiency syndrome (AIDS)	E2
	E4	+	Worst prognosis
Hepatitis C virus	E2		E3 and E2: ↑ Risk chronic infection
	E4			(Lowest response to antiviral therapy)
OTHER [TRAUMATIC BRAIN INJURY (Lichtman et al., 2000; Chamelian et al., 2004; Crawford et al., 2009; Hiekkanen et al., 2009; Ponsford et al., 2011); DIABETES MELLITUS (Tsuzuki et al., 1998; Bedlack et al., 2003; Saito et al., 2004; Yin et al., 2013); CANCER (Ahles et al., 2003; Porrata-Doria et al., 2010; Kulminski et al., 2011; Saadat, 2012); DEPRESSION (Irie et al., 2008; Kim et al., 2010, 2011; Meng and D'Arcy, 2013)]
Traumatic brain injury	E2
	E4		Worst prognosis
Diabetes mellitus	E2
	E4		↑ Risk diabetic neuropathy	Best response to low fat diet
Cancer	E2
	E4	(+)		(E4: ↑ side effect following chemotherapy)
Depression	E2
	E4		↑ Risk dementia

Creutzfeldt-Jakob disease, gallbladder stone disease, Huntington's disease, inclusion-body myositis, cerebral palsy, progressive supranuclear palsy, temporal lobe epilepsy multiple system atrophy, multiple sclerosis, frontotemporal dementia, malaria and herpes simplex virus need further exploration (Bu, 2009; Leduc et al., 2011; Verghese et al., 2011; Xue et al., 2012; Yin et al., 2012; Rubino et al., 2013; Wei et al., 2014).

^*In subarachnoid hemorrhage and intracerebral hemorrhage stroke;

+, increased risk; −, decreased risk; (parentheses), limited, or conflicting results exist.