A Study in Healthy Participants to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma

• JNJ-54175446 (Drug): Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.
• Placebo (Drug): Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2.

Primary outcomes

• The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma [Part 1: Up to Day 2]
• The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Plasma [Part 2: Up to Day 8]
• The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF) [Part 1: Up to Day 2]
• The Effects of JNJ-54175446 (Dose Response) on Levels of Aβ Fragments in Cerebrospinal Fluid (CSF) [Part 2: Up to Day 8]
• The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood [Part 1: Up to Day 2]
• The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in Blood [Part 2: Up to Day 8]
• The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF [Part 1: Up to Day 2]
• The Effects of JNJ-54175446 (Dose Response) on Markers of (Neuro)Inflammation / Protection in CSF [Part 2: Up to Day 8]
• Maximum Observed Plasma Concentration (Cmax) After Single- and Multiple-Dose Administration [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• Minimum Observed Plasma Concentration (Cmin)During Dosing Interval [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• The Observed Plasma Concentration Just Prior to the Beginning or at the end of a Dosing Interval of any Dose Other Than the First Dose (Ctrough) [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• Average Plasma Concentration at Steady State Over the Dosing Interval (Cavg) [Part 1: Day 1 - Day 2; Par 2: Day 1, Day 2 to 6, Day 7, Day 8]
• Time to Reach the Maximum Plasma Concentration, After Single- and Multiple-Dose Administration (Tmax) [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• Area Under The Concentration-Time Curve From 0 To t Hours Postdosing (AUCt) [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• Area Under the Concentration-Time Curve From 0 to 24 Hours Postdosing (AUC24h) [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]
• The Ratio of the Maximum Plasma Concentration (Peak) to Trough Observed Concentration (Peak/Trough Ratio) [Part 1: Day 1 - Day 2; Part 2: Day 1 to Day 8]

Secondary outcomes

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability [Screening up to follow-up (in part 1 and part 2 [approximately up to 8 weeks])]

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

* Participants must have a body mass index (BMI) between 18 and 32 kilogram (kg)/ meter (m)\^2, inclusive (BMI = weight/height\^2)
* Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG)

Part 1 and 2 (Elderly Participants):

* Healthy male or female participants between 55 and 75 years of age, inclusive
* Participant must be healthy on the basis of both physical and neurological examination performed at Screening and at admission to the clinical unit

Part 1 (Young Participants):

\- Healthy male participants between 18 and 45 years of age, inclusive

Exclusion Criteria:

* Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant
* Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening (per Screening evaluations)
* Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening (per Screening evaluations)
* Participant has a history of malignancy within 5 years before Screening
* Participant has signs of increased intracranial pressure based on fundoscopy at Screening

• Results publication: Triana-Baltzer G, Timmers M, De Boer P, Schoene M, Furey M, Bleys C, Vrancken I, Slemmon R, Ceusters M, van Nueten L, Kolb H. Profiling classical neuropsychiatric biomarkers across biological fluids and following continuous lumbar puncture: A guide to sample type and time. Compr Psychoneuroendocrinol. 2022 Jan 15;10:100116. doi: 10.1016/j.cpnec.2022.100116. eCollection 2022 May. PMID 35774109

• Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC

NIH grants: 2016