We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Editorial |

CSF Biomarkers for Secondary Prevention Trials Why Markers of Amyloid Deposition and Neurodegeneration Are Both Important

David M. Holtzman, MD
Arch Neurol. 2012;69(6):691-692. doi:10.1001/archneurol.2012.587.
Text Size: A A A
Published online


A major challenge in developing therapies for Alzheimer disease (AD) as well as most neurodegenerative diseases is that by the time even the earliest clinically detectable signs and symptoms of the disease are apparent, there is already substantial brain injury.13 Most therapeutic trials in AD that are intended to address fundamental molecules and mechanisms underlying the disease have been performed in individuals who have mild to moderate dementia. A few trials have targeted people with very mild dementia/mild cognitive impairment believed to be due to AD. However, recent studies suggest that the use of cerebrospinal fluid (CSF) and amyloid imaging can detect the presence of amyloid-β (Aβ) deposition beginning as early as 10 to 15 years prior to the onset of any clinically detectable cognitive decline owing to AD.1,2,49 In addition, evidence of neurodegeneration and tauopathy appear to begin approximately 5 years prior to the cognitive decline that characterizes early AD.1,2,49 If both academic groups and the pharmaceutical industry are going to move toward prevention trials to delay the onset of cognitive impairment and dementia, biomarkers will need to be used to select people who are clinically normal but at high risk for near-term cognitive decline. Without such an approach, trial size will be enormous and cost prohibitive, and individuals may be subjected to treatments that have the potential for toxicity with no clear benefit.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

1 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections