A Study to Evaluate ALN-5288 in Patients With Alzheimer's Disease

Inclusion Criteria:

• Is able and willing to meet all study requirements in the opinion of theInvestigator

• Has a diagnosis of Alzheimer's disease (AD) based on clinical findings supported bycerebrospinal fluid (CSF) biomarkers or positive positron emission tomography (PET)amyloid imaging within 7 years prior to screening

• Has mild cognitive impairment (MCI) or dementia due to AD

Exclusion Criteria:

• Has non-AD dementia

• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upperlimit of normal (ULN)

• Has total bilirubin >1.5×ULN

• Has known human immunodeficiency virus infection

• Has history of hepatitis C virus or current hepatitis B virus infection

• Has systolic blood pressure >160 mmHg and/or a diastolic blood pressure >100 mmHgafter 10 minutes of rest at screening

• Has an estimated glomerular filtration (eGFR) of <45 mL/min/1.73 m^2 at screening

• Has clinically significant ECG abnormalities at screening

• Has uncontrolled psychiatric disease, including patients deemed by the Investigatorto be at significant risk of suicide, major depressive episode, psychosis,confusional state, or violent behavior

• Has history of bleeding diathesis or coagulopathy due to chronic conditions

• Has a medical history of brain or spinal disease that would interfere with the ITinjection and LP procedures

• Has history of uncontrolled seizures within the last 6 months prior to Screening