A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease

The purpose of this study is to evaluate the long-term safety and tolerability of JNJ-54861911 during 6 months of treatment in participants with early (predementia) alzheimer's disease (AD \[degenerative disease of the brain characterized by the insidious onset of dementia, impairment of memory, judgment, attention span, and problem solving skills are followed by severe apraxias and a global loss of cognitive abilities\]).

This is a double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect), randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), parallel-group study. The study consists of 3 Parts; Screening Phase of 90 days, double-blind Treatment Phase of 6 months and Follow-up Phase of 7 to 28 days following the last dose in Month 6. Eligible participants in the early (predementia) AD spectrum will be randomized to either Treatment group 1, 2 or placebo and participants who previously participated in study 54861911ALZ1005 will be enrolled in this study and will receive the same treatment as in study 54861911ALZ1005. The study duration for each participant will be approximately 10 months. Blood and cerebrospinal fluid (CSF) samples will be collected to evaluate the plasma pharmacokinetics of JNJ-54861911, as well as amyloid beta fragments. Participants' safety will be monitored throughout the study, including magnetic resonance imaging (MRI) and cognitive measures.

Eligibility Criteria:
Inclusion Criteria:

* Participants in the early alzheimer's disease (AD) spectrum must have a global Clinical Dementia Rating Scale( CDR) score of 0 (asymptomatic at risk for AD) to 0.5 prodromal AD (pAD) inclusive
* Participants must have evidence of amyloid pathology 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
* Participants must have a body mass index between 18 and 35 kilogram per square meter (kg/m\^2), inclusive, at screening
* Participants 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 ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population and not a potential cause of cognitive impairment, with written concurrence with the sponsor's medical monitor
* Before randomization, a woman must be not of childbearing potential: postmenopausal (greater than or equal to \[\>=\] 50 years of age with amenorrhea for at least 12 months; permanently sterilized \[e.g., tubal occlusion, hysterectomy, bilateral salpingectomy\]); or otherwise be incapable of pregnancy. In case of questionable status qualified personal of the sponsor should be consulted to decide on the potential for inclusion of the participant

Exclusion Criteria:

* Participant has evidence of any brain disease, other than potential very early signs of AD (e.g. 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 strokes including lacuna's (as imaged by cerebral MRI) and Major Depression (as defined by most current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria)
* Participant has evidence of familial autosomal dominant AD. (Inclusion can be made upon written confirmation by sponsor, when the mutation is known and deemed not to be modulating Beta-secretase \[BACE\] cleavage)
* Participant with history or presence of significant depression as defined by the most current DSM criteria
* Participant has a clinically significant abnormal physical- or neurological examination, vital signs at screening or baseline (Day 1 predose)
* Participant has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. unstable situation needing monitoring or regular dose adaptations)