Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease

Patient inclusion criteria:

• Diagnosis AD in early phase according to the IWG-2 criteria.

• Mini-Mental State Examination (MMSE) Score ≥20.

• In-vivo evidence of Alzheimer´s pathology (one of the following):

• Decreased Aβ42 together with increased t-tau or p-tau in CSF.

• Increased tracer retention on amyloid PET.

• Availability of a next of kin who knows the patient well and is willing to accompanythe subject to all trial visits and give information about the patients functionallevel.

• Signed informed consent.

• The patient is judged fitted for the study and capable to cooperate in treatment andfollow-up.

• Ability to communicate in Norwegian or another Scandinavian language.

Patient exclusion criteria:

• Pregnancy or unwilling to use adequate birth control for the duration of and 6months beyond study participation. Defined according to Clinical Trial FacilitationGroup document "Recommendations related to contraception and pregnancy testing inclinical trials".

• Positive for Hepatitis B, Hepatitis C or HIV at screening.

• Not qualified to give consent at inclusion.

• Any other condition judged to interfere with the safety of the patient or the intentand conduct of the study.

Related to medical history:

• Stroke

• Anaphylaxis

• Prior adverse reaction to any human blood product

• Any history of a blood coagulation disorder or hypercoagulability

• Congestive heart failure, defined as any previous heart failure hospitalization, orcurrent symptomatic heart failure in New York heart Association class ≥II withreduced, mid-range or preserved ejection fraction.

• Coagulation defect or hypercoagulopathy

• Uncontrolled hypertension

• Renal failure

• Prior intolerance to intravenous fluids

• Recent history of uncontrolled atrial fibrillation

• Bone marrow transplant

• IgA deficiency

• Severe protein S deficiency

• Thrombocytopenia (platelets < 40 x 10 to the power of 9/L)

• Contraindication for Octaplasma

Related to medications or other treatments:

• Any concurrent use of anticoagulant therapy, clopidogrel or acetylsalicylicacid/Dipyridamol in combination.

• Initiation or change in the dosage of a acetylcholine esterase inhibitor (AChEI) ormemantine during the trial (week 0-52). Participants will be urged to start on AChEIwhen diagnosis is communicated, and must be on a stable dose for at least one monthprior to screening.

• Concurrent participation in another treatment trial for AD. If there was priorparticipation, the last dose of the investigational agent must have been given atleast 6 months prior to screening, except if the patient received placebomedication.

• Treatment with any human blood product, including intravenous immunoglobulin, duringthe 6 months prior to screening or during the trial.

• Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics,long-acting opioids, or other medications that is judged to interfere withcognition. Intermittent treatment with short-acting benzodiazepines or atypicalantipsychotics may be permitted, provided that no dose is administered within 72hours prior to cognitive assessment.

Related to magnetic resonance imaging:

• Claustrophobia

• Any metallic surgical implant, like a pacemaker or clip that is incompatible withMRI.

Certain metallic implants like joint replacements may be permitted, provided that specific manufacturer specifications are available, and that the device is known to be safe for 7T MRI. In case a patient is not eligible for the 7T scanner, the 3T scanner will be used.