Determine safety of plasma infusion or exchange in APOE 44 patients.

Inclusion criteria

• Patient age 50 to 75.
• APOE 44 homozygote.
• Meets the Petersen criteria for MCI (41).
• Clinical Dementia Rating (CDR) of 0.5 and Mini Mental Status Examination (MMSE) of 24 to 30 inclusive.
• Has an informant who the investigator judges has sufficient patient contact to provide accurate information.
• Stable depression and or anxiety.
• Stable psychoactive medication for 6 weeks.

Exclusion criteria

• History of severe reaction to plasma or plasma derived products which include but not limited to severe allergic reaction, anaphylactic reaction and transfusion related acute lung injury (TRALI).
• Patients who do not want to receive blood transfusion for religious or cultural reasons such as Jehovah Witness Faith.
• Has a medical condition that would interfere with participation such as congestive heart failure (New York Heart Association Class III or IV), unstable angina, moderate to severe renal impairment, liver failure, and poorly controlled diabetes.
• History of autoimmune disease considered clinically significant or requiring chronic steroid or immune suppression medication.
• History of being HIV +.
• History of +VE test result indicating active hepatitis C or B (defined as both hepatitis B surface antigen and hepatitis core antibody +VE).
• Uncontrolled hypertension as defined by systolic/diastolic BP three times more than 165/100.
• No venous access for plasma exchange therapy.
• Any neurological condition that could be contributing to cognitive decline such as Lewy body disease, front temporal dementia, strokes or other cerebrovascular disease, head trauma, substance abuse, multiple sclerosis, Vitamin B12 deficiency, thyroid deficiency.
• Epileptic seizures within 10 years of screening.
• Cancer diagnosis (other than non-melanoma skin cancer) in the last 5 years.
• More than 1 subcortical stroke or more than 1 cortical stroke.
• Unable to have an MRI.
• MRI showing acute or subacute hemorrhage, evidence of normal pressure hydrocephalus, hemispheric infarcts, glioma or other brain tumor that could contribute to cognitive decline.
• Unstable psychiatric condition.
• On another experimental treatment study or has been on one in the last 3 months.
• If a patient consents to lumbar puncture (LP), they will be excluded from LP if any contraindication to having an LP is present. Examples are platelet count<100,000, spine deformity or contraindication to come off blood thinner for the LP. Patients may still participate in the rest of the study without having and LP.
• Any unspecified reason that the investigator finds the patient unsuitable to take part.