Innate Immunity Stimulation Via TLR9 in Early AD

This single-center, double-blind, placebo-controlled study will recruit in total 39 participants with either Mild Cognitive Impairment due to Alzheimer's disease (MCI) or Mild Alzheimer's disease dementia (mild AD). There will be 3 Dose levels. An initial cohort of 13 subjects will be randomized to a Dose level 1 (0.1 mg/kg vs. placebo) lasting 8 weeks. An additional 13 subjects will be recruited and randomized into Dose level 2 (0.25 mg/kg vs. placebo) for 8 weeks and 13 subjects for the last Dose level 3 (0.5 mg/kg vs. placebo) for 8 weeks. The primary objective will be to assess safety and tolerability of CpG 1018.

Inclusion Criteria:65-85 years of ageMCI due to AD or mild AD dementia per NIA-AA specified criteria published in 2018Montreal Cognitive Assessment (MoCA) score ≥17 AND;Positive Florbetaben PET amyloid scan, or other positive PET amyloid scan performed within one year of study enrollmentMust be able to provide consent or assent (If applicable).Must be willing and able to participate in all study related procedures.Must have a reliable study partner to provide information on the subject's cognitive and functional status. Study partner must have sufficient contact with the subject, as determined by the PI, and be available to accompany the subject to clinic visits or by phone.Exclusion Criteria:History of psychiatric illness (e.g. hallucinations, major depression, suicidal ideation or delusions) that could interfere with completion of study related procedures as determined by PIHistory of autoimmune disorders or antibody-mediated disease, severe asthma, or other serious infection or systemic illness, as determined by PIUse of corticosteroids or immunosuppressive drugs within 30 days of study entryHistory of splenectomyRenal impairmentUse of chloroquine within 8 weeks of study entryInability to undergo MRI imagingHistory of TIA, stroke or seizures within 12 months of screeningAny neurological condition other than AD that could contribute to cognitive impairment (including related to possible "long COVID") as determined by PIParticipation in any other current AD investigational interventional trialCurrent use of an anti-coagulantCurrent use of drugs that are major substrates of cytochrome P450 (CYP) enzyme 1A2Recent exposure to COVID-19 infection within 14 days or recent onset of symptoms within 14 days that may be related to COVID-19 infection