Effects of Sleep Deprivation on Cerebrospinal Fluid (CSF) Amyloid-beta (Aβ) Dynamics

Losing Sleep Over Alzheimer's Disease? Effects of Sleep Deprivation on Cerebrospinal Fluid Amyloid-beta Dynamics

Introduction: Alzheimer's disease (AD) is characterized by neurodegeneration of the brain in the form of neurofibrillary tangles and plaques containing the amyloid-beta protein (Abeta). Recent animal studies have shown that extended wakefulness is associated with increased production of these Abeta proteins and that sleep leads to a marked fall in their production.

Aim: The investigators aim to distinguish a similar effect of sleep disturbance on cerebrospinal fluid (CSF) Abeta levels in humans, which may point out sleep disturbance as an important factor in AD development.

Methods: a study in 26 healthy male volunteers, measuring CSF Abeta levels during a sleep deprivation night and before and after a control night with unrestricted sleep.

Expected results: The investigators expect sleep deprivation to lead to an increase in CSF Abeta levels, as compared to the levels in the control night.

Inclusion Criteria:

• Written informed consent
• Age 40-60 years
• Male
• Subject is in good health as established by medical history, physical examination, ECG and laboratory examination
• Laboratory parameters (as described on in section 3.7 screening) should be within the normal ranges as applicable in RUNMC, Nijmegen, or clinically acceptable to the investigator
• Normal sleep behaviour, Pittsburg Sleep Quality index score ≤5
• MMSE 28 or higher
• Medication free

Exclusion Criteria:

• Presence of blood coagulopathy, established by medical history
• Allergy to local anesthetic agents
• Contra-indication for spinal catheter placement: medical history of compression of spinal cord, spinal surgery, skin infection, developmental abnormalities in lower spine
• Subjects who are currently participating in another study or have participated in a clinical study within 30 days, based on their own report about participation history
• Subjects with a history of drug or alcohol abuse
• Subjects who are part of the study staff personnel or family members of the study staff personnel