Making Antibody Treatments More Effective in Early Alzheimer's Disease Using 3Tesla Magnetica Resonance

Inclusion criteria

1Participant is willing and able to give informed consent for participation in the study.

• Participant is eligible for anti-amyloid therapy (AAT), i.e.:

• Participants aged 30-90.
• Diagnosis of early symptomatic AD, including MCI or mild dementia [2].
• Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
• Confirmed amyloid pathology through CSF or PET imaging. 3. Participant is willing to start Anti-amyloid therapy as part of his/her clinical-practice- therapeutic plan.

• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional four weeks after the end of study.

• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

Exclusion criteria

• 1. Contraindications to AAT, including:

• Significant neurological diseases other than AD that could affect cognition or study participation (e.g., other dementias, serious brain infections, Parkinson's disease, multiple concussions, epilepsy with recurrent seizures).
• Homozygous ApoE4 genotype.
• Current use of anticoagulant therapy.
• Vascular abnormalities: Presence of more than 4 microhemorrhages (defined as ≤10 mm in greatest diameter), a single macrohemorrhage >10 mm, superficial siderosis, evidence of vasogenic edema, multiple lacunar infarcts, or stroke involving a major vascular territory.
• Amyloid-Related Imaging Abnormalities (ARIA): Evidence of ARIA, including cerebral amyloid angiopathy-related inflammation (CAA-ri) or amyloid beta-related angiitis (ABRA).
• Bleeding disorders: History of bleeding disorders not under adequate control, including a platelet count <50,000 or international normalized ratio (INR) >1.5 for participants not on anticoagulant therapy.
• Being currently under treatment with another AAT other than lecanemab/donanemab (e.g. as part of a Clinical Trial).

• Current serious or unstable illnesses, including:
• Cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic diseases.
• Conditions that, in the clinician's opinion, could interfere with study analyses or with a life expectancy of less than 24 months.
• History of cancer within the last 5 years, except for non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence.

• Inability to undergo MRI or PET imaging procedures (e.g. non-MRI safe pacemaker or devices, claustrophobia etc).

• Women of childbearing potential who are not using adequate contraception, as well as pregnant or breastfeeding women.