An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia

This is a randomized (study drug assigned by chance), double-blind (neither the researchers
nor the participants know what treatment the participant is receiving), multi-center (more
than one hospital or medical school team work on a medical research study),
placebo-controlled, parallel-group study in participants who are asymptomatic and at risk for
developing Alzheimer's dementia. The study will consist of a Screening Phase (approximately
90 days), treatment Phase (54 months) and follow-up Phase (7 to 28 days). In treatment Phase
eligible Participants will be randomized to receive study drug or placebo once daily for up
to 4.5 years. The maximum study duration for a participant will be 58 months. Participants'
safety will be monitored throughout the study.

Inclusion Criteria:

- Participant must have a global Clinical Dementia Rating Scale- (CDR) score of '0' at
Screening

- Participants 60 to 64 years of age must also have 1 of the following 3 conditions: a)
a positive family history for dementia (minimum of 1 first degree relative), b) a
previously known apolipoprotein E, ε4 allele (APOE ɛ4) genotype, c) a previously known
biomarker status demonstrating elevated amyloid accumulation in cerebrospinal fluid
(CSF) or positron emission tomography (PET)

- Participant must be able to read and write and must have adequate hearing and visual
acuity to complete the psychometric tests. The legally acceptable representative must
also be able to read and write

- Participants must have evidence of amyloid accumulation by means of either: a) low
Cerebrospinal Fluid (CSF) ABeta 1-42 levels at Screening; b) a positive amyloid
positron emission tomography (PET) scan at Screening (depending on the site's PET
capability) by visual read

- Participant must be otherwise healthy for their age group or medically stable with or
without medication on the basis of physical examination, medical history, vital signs,
and 12-lead electrocardiogram (ECG) performed at Screening or at Baseline

Exclusion Criteria:

- Participant is receiving an acetylcholinesterase (AChE) inhibitor and/or memantine at
any time during Screening or Day 1 predose

- Participant has evidence of any brain diseases, other than potential very early signs
of Alzheimer's Dementia (AD) (example. mild hippocampal atrophy) or typical
age-related changes (e.g. mild white matter hyperintensity on magnetic resonance
imaging [MRI]) or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that
could explain a possible cognitive deficit (including, but not limited to vascular
encephalopathy or large strokes (as imaged by cerebral MRI)

- Participant has any contraindications for MRI (example, prostheses, implants,
claustrophobia, pacemaker)

- Participant has met criteria for dementia or has a brain disorder that can cause
dementia

- Participant has evidence of familial autosomal dominant AD (mutation identified in the
family and/or participant prior to randomization)