Biomarkers for Dementia 

Detection and Research 

FACT SHEET 

n Types of Biomarkers and Tests 

– Brain Imaging 

– Cerebrospinal Fluid Biomarkers 

– Other Types 

n Use in Diagnosis 

n Use in Research 

n The Future of Biomarkers 

n How You Can Help 

n For More Information 

Biomarkers for Dementia 

— Get the Facts 

Biomarkers are measures of 

what is happening inside the 

living body, shown by the 

results of laboratory and imaging 

tests. Biomarkers can help doctors 

and scientists diagnose diseases and 

health conditions, find health risks 

in a person, monitor responses to 

treatment, and see how a person’s 

disease or health condition changes 

over time. For example, an increased 

level of cholesterol in the blood is a 

biomarker for heart-attack risk. 

Many types of biomarker tests are 

used for research on Alzheimer’s 

disease and related dementias. 

Changes in the brains of people with 

these disorders may begin many 

years before memory loss or other 

symptoms appear. Researchers use 

biomarkers to help detect these brain 

changes in people, who may or may 

not have obvious changes in memory 

or thinking. Finding these changes 

early in the disease process helps identify 

people who are at the greatest risk 

of Alzheimer’s or another dementia 

and may help determine which people 

might benefit most from a particular 

treatment. 

Use of biomarkers in clinical settings, 

such as a doctor’s office, is limited 

at present. Some biomarkers may 

be used to identify or rule out 

causes of symptoms for some people. 

Researchers are studying many types 

of biomarkers that may one day be 

used more widely in doctors’ offices 

and other clinical settings. 

Types of Biomarkers 

and Tests 

In Alzheimer’s disease and related 

dementias, the most widely used 

biomarkers measure changes in the 

size and function of the brain and 

Alzheimer’s and related Dementias 

Education and Referral Center 
its parts, as well as levels of certain 

proteins seen on brain scans and in 

cerebrospinal fluid and blood. 

Brain Imaging 

Brain imaging, also called brain scans, 

can measure changes in the size of the 

brain, identify and measure specific brain 

regions, and detect biochemical changes 

and vascular damage (damage related to 

blood vessels). In clinical settings, doctors 

can use brain scans to find evidence of 

brain disorders, such as tumors or stroke, 

that may aid in diagnosis. In research 

settings, brain imaging is used to study 

structural and biochemical changes in the 

brain in Alzheimer’s disease and related 

dementias. There are several types 

of brain scans. 

Computerized Tomography 

What is it? 

A computerized tomography (CT) scan 

is a type of X-ray that uses radiation to 

produce images of the brain. A CT can 

show the size of the brain and identify 

a tumor, stroke, head injury, or other 

potential cause of dementia symptoms. 

CT scans provide greater detail than 

traditional X-rays, but a less detailed 

picture than magnetic resonance imaging 

(MRI) and cannot easily measure changes 

over time. Sometimes a CT scan is used 

when a person can’t get an MRI due to 

metal in their body, such as a pacemaker. 

What’s the procedure like? 

During a CT scan, a person lies in a 

scanner for 10 to 20 minutes. A donutshaped device moves around the head 

to produce the image. 

What does it show? 

A head CT can show shrinkage of brain 

regions that may occur in dementia, as 

well as signs of a stroke or tumor. 

When is it used? 

A CT is sometimes used to help a doctor 

diagnose dementia based on changes 

in the size of particular brain regions, 

compared either to an earlier scan or to 

what would be expected for a person of 

the same age and size. It is rarely used in 

the research arena to study Alzheimer’s 

disease and related dementias. 

Magnetic Resonance Imaging 

What is it? 

Magnetic resonance imaging (MRI) 

uses magnetic fields and radio waves 

to produce detailed images of body 

structures, including the size and shape 

of the brain and brain regions. MRI 

may be able to identify some causes of 

dementia symptoms, such as a tumor, 

stroke, or head injury. MRI may also 

show whether areas of the brain have 

atrophied, or shrunk. 

What’s the procedure like? 

During an MRI, a person lies still in 

a tunnel-shaped scanner for about 30 

minutes for diagnostic purposes and up 

to 2 hours for research purposes. MRI is 

a safe, painless procedure that does not 

involve radioactivity. The procedure is 

noisy, so people are often given earplugs 

or headphones to wear. Some people 

become claustrophobic and anxious inside 

an MRI machine, which can be addressed 

with anxiety-relieving medication taken 

shortly before the scan. 

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Because MRI uses strong magnetic fields 

to obtain images, people with certain 

types of metal in their bodies, such as a 

pacemaker, surgical clips, or shrapnel, 

cannot undergo the procedure. 

What does it show? 

MRI scans provide pictures of brain 

structures and whether abnormal 

changes, such as shrinkage of 

areas of the brain, are present. 

Evidence of shrinkage may support a 

diagnosis of Alzheimer’s or another 

neurodegenerative dementia but 

cannot indicate a specific diagnosis. 

Researchers use different types of 

MRI scans to obtain pictures of brain 

structure, chemistry, blood flow, and 

function, as well as the size of brain 

regions. MRI also provides a detailed 

picture of any vascular damage in the 

brain — such as damage due to a stroke 

or small areas of bleeding — that may 

contribute to changes in cognition. 

Repeat scans can show how a person’s 

brain changes over time. 

When is it used? 

Doctors often use MRI scans to identify 

or rule out causes of memory loss, such 

as a stroke or other vascular brain injury, 

tumors, or hydrocephalus. These scans 

also can be used to assess brain shrinkage. 

In the research arena, various types 

of MRI scans are used to study the 

structure and function of the brain in 

aging and Alzheimer’s disease. In clinical 

trials, MRI can be used to monitor the 

safety of novel drugs and to examine how 

treatment may affect the brain over time. 

Positron Emission Tomography 

What is it? 

Positron emission tomography (PET) 

uses small amounts of a radioactive 

substance, called a tracer, to measure 

specific activity — such as glucose (energy) 

use — in different brain regions. Different 

PET scans use different tracers. PET 

is commonly used in dementia research 

but less frequently in clinical settings. 

What’s the procedure like? 

The person having a PET scan receives 

an injection of a radioactive tracer into a 

vein in the arm, then lies on a cushioned 

table, which is moved into a donut-shaped 

scanner. The PET scanner takes pictures 

of the brain, revealing regions of normal 

and abnormal chemical activity. A PET 

scan is much quieter than MRI. The 

entire process, including the injection 

and scan, takes about 1 hour. 

The amount of radiation exposure 

during a PET scan is relatively low. 

People who are concerned about 

radiation exposure or who have had 

many X-rays or imaging scans should 

talk with their doctor. 

What does it show? 

Fluorodeoxyglucose (FDG) PET scans 

measure glucose use in the brain. 

Glucose, a type of sugar, is the primary 

source of energy for cells. Studies show 

that people with dementia often have 

abnormal patterns of decreased glucose 

use in specific areas of the brain. An 

FDG PET scan can show a pattern that 

may support a diagnosis of a specific 

cause of dementia. 

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Medical Imaging App 

Learn more about different types 

of imaging, including CT, MRI, and 

PET scans, with the Understanding 

Medical Exams app from the National 

Institute of Biomedical Imaging and 

Bioengineering. Visit www.nibib.nih.gov/

Understanding-Medical-Scans-App.

Amyloid PET scans measure abnormal 

deposits of a protein called beta-amyloid. 

Higher levels of beta-amyloid are consistent with the presence of amyloid plaques, 

a hallmark of Alzheimer’s disease. Several 

tracers may be used for amyloid PET 

scans, including florbetapir, flutemetamol, 

florbetaben, and Pittsburgh compound B. 

Tau PET scans detect abnormal 

accumulation of a protein, tau, which 

forms tangles in nerve cells in Alzheimer’s 

disease and many other dementias. 

AV-1451 is a tau tracer that can help 

identify the presence of tau tangles in 

the brain. Several other tau tracers, 

such as PI-2620 and MK-6240, are 

also being studied in clinical trials and 

other research settings. 

When is it used? 

In clinical care, FDG PET scans may 

be used if a doctor strongly suspects 

frontotemporal dementia as opposed 

to Alzheimer’s dementia based on the 

person’s symptoms, or when there is an 

unusual presentation of symptoms. 

Amyloid PET imaging is sometimes 

used by medical specialists to help with 

a diagnosis when Alzheimer’s disease 

is suspected but uncertain, even after 

a thorough evaluation. Amyloid PET 

imaging may also help with a diagnosis 

when people with dementia have unusual 

or very mild symptoms, an early age of 

onset (under age 65), or any of several 

different conditions, such as severe 

depression, that may contribute to 

dementia symptoms. A negative amyloid 

PET scan rules out Alzheimer’s disease. 

Tau PET scans may be used to monitor 

progression of Alzheimer’s disease. 

In research, amyloid and tau PET scans 

are used to determine which individuals 

may be at greatest risk for developing 

Alzheimer’s disease, to identify clinical 

trial participants, and to assess the 

impact of experimental drugs designed 

to affect amyloid or tau pathways. 

Cerebrospinal Fluid Biomarkers 

Cerebrospinal fluid (CSF) is a clear 

fluid that surrounds the brain and 

spinal cord, providing protection and 

insulation. CSF also supplies numerous 

nutrients and chemicals that help keep 

brain cells healthy. Proteins and other 

substances made by cells can be detected 

in CSF, and their levels may change 

years before symptoms of Alzheimer’s 

and other brain disorders appear. 

Lumbar Puncture 

What is it? 

CSF is obtained by a lumbar puncture, 

also called a spinal tap, an outpatient 

procedure used to diagnose several types 

of neurological problems. 

What’s the procedure like? 

People either sit or lie curled up on their 

side while the skin over the lower part 

of the spine is cleaned and injected with 

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a local anesthetic. A very thin needle is 

then inserted into the space between the 

bones of the spine. CSF either drips out 

through the needle or is gently drawn out 

through a syringe. The entire procedure 

typically takes 30 to 60 minutes. 

After the procedure, the person lies 

down for a few minutes and may receive 

something to eat or drink. People can 

drive themselves home and resume 

regular activities, but they should 

refrain from strenuous exercise for 

about 24 hours. 

Some people feel brief pain during 

the procedure, but most have little 

discomfort. A few may have a mild 

headache afterward, which usually 

disappears after taking a pain reliever 

and lying down. Sometimes, people 

develop a persistent headache that gets 

worse when they sit or stand. This type 

of headache can be treated with a blood 

patch, which involves injecting a small 

amount of the person’s blood into his or 

her lower back to stop a leak of CSF. 

Certain people cannot have a lumbar 

puncture, including people who take 

medication such as warfarin to thin their 

blood, have a low platelet count or an 

infection in the lower back, or have had 

major back surgery. 

What does it show? 

The most widely used CSF biomarkers 

for Alzheimer’s disease measure certain 

proteins: beta-amyloid 42 (the major 

component of amyloid plaques in the 

brain), tau, and phospho-tau (major 

components of tau tangles in the brain). 

In Alzheimer’s disease, beta-amyloid 

42 levels in CSF are low, and tau and 

phospho-tau levels are high, compared 

with levels in people without Alzheimer’s 

or other causes of dementia. 

When is it used? 

In clinical practice, CSF biomarkers may 

be used to help diagnose Alzheimer’s, for 

example, in cases involving an unusual 

presentation of symptoms or course of 

progression. CSF also can be used to 

evaluate people with unusual types of 

dementia or with rapidly progressive 

dementia. 

In research, CSF biomarkers are 

valuable tools for early detection of a 

neurodegenerative disease. They are 

also used in clinical trials to assess the 

impact of experimental medications. 

Other Types of Biomarkers 

Blood Tests 

Proteins that originate in the brain, 

such as tau and beta-amyloid 42, may 

be measured with sensitive blood tests. 

Levels of these proteins may change 

because of Alzheimer’s, a stroke, or 

other brain disorders. These blood 

biomarkers are less accurate than CSF 

biomarkers for identifying Alzheimer’s 

and related dementias. However, new 

methods to measure these brain-derived 

proteins, particularly beta-amyloid 42/ 

beta-amyloid 40 and phospho-tau 181, 

have improved, suggesting that blood 

tests may be used in the future for 

screening and perhaps diagnosis. 

Many other proteins, lipids, and other 

substances can be measured in the 

blood, but so far none has shown value 

in diagnosing Alzheimer’s. 

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Currently, dementia researchers use 

blood biomarkers to study early detection, 

prevention, and the effects of potential 

treatments. They are not used in doctors’ 

offices and other clinical settings. 

Genetic Testing 

Genes are structures in a body’s cells 

that are passed down from a person’s 

birth parents. They carry information 

that determines a person’s traits and 

keep the body’s cells healthy. Problems 

with genes can cause diseases like 

Alzheimer’s. 

A genetic test is a type of medical test 

that analyzes DNA from blood or saliva 

to determine a person’s genetic makeup. 

A number of genetic combinations may 

change the risk of developing a disease 

that causes dementia. 

Genetic tests are not routinely used in 

clinical settings to diagnose or predict 

the risk of developing Alzheimer’s or a 

related dementia. However, a neurologist 

or other medical specialist may order a 

genetic test in rare situations, such as 

when a person has an early age of onset 

or a strong family history of Alzheimer’s 

or a related brain disease. A genetic 

test is typically accompanied by genetic 

counseling for the person before the test 

and when results are received. Genetic 

counseling includes a discussion of the 

risks, benefits, and limitations of test 

results. 

Genetic testing for APOE e4, the 

main genetic risk factor for late-onset 

Alzheimer’s disease, is available as 

a direct-to-consumer or commercial 

test. It is important to understand 

that genetic testing provides only one 

piece of information about a person’s 

risk. Other genetic and environmental 

factors, lifestyle choices, and family 

medical history also affect a person’s 

risk of developing Alzheimer’s disease. 

In research studies, genetic tests 

may be used, in addition to other 

assessments, to predict disease risk, 

help study early detection, explain 

disease progression, and study whether 

a person’s genetic makeup influences 

the effects of a treatment. 

Read more about Alzheimer’s disease 

genetics at www.nia.nih.gov/health/ 

topics/genes-and-genetics. 

Biomarkers in Development 

Researchers are studying other biomarker 

tests for possible use in diagnosing and 

tracking Alzheimer’s disease and other 

types of dementia. These biomarkers 

include reduced ability to smell, the 

presence of certain proteins in the retina 

of the eye, and other proteins that indicate 

the health of neurons. At this point, 

doctors do not use these biomarkers to 

diagnose dementia. 

Biomarkers in Dementia 

Diagnosis 

Some biomarkers may be part of a 

diagnostic assessment for people 

with symptoms of Alzheimer’s or a 

related dementia. Other parts of the 

assessment typically include a medical 

history; physical exam; laboratory tests; 

neurological tests of balance, vision, 

and other cognitive functions; and 

neuropsychological tests of memory, 

problem solving, language skills, and 

other mental functions. 

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Different biomarkers provide different 

types of information about the brain 

and may be used in combination with 

each other and with other clinical tests 

to improve the accuracy of diagnosis — 

for example, in cases where the age of 

onset or progression of symptoms is 

not typical for Alzheimer’s or a related 

brain disorder. 

Physicians with expertise in Alzheimer’s 

disease and related dementias are 

the most appropriate clinicians to 

order biomarker tests and interpret 

the results. These physicians include 

neurologists, geriatric psychiatrists, 

neuropsychologists, and geriatricians. 

Currently, Medicare and other health 

insurance plans cover only certain, 

limited types of biomarker tests for 

dementia symptoms, and their use 

must be justified based on the person’s 

symptoms and specific criteria. 

Read more about diagnosing dementia 

at www.nia.nih.gov/health/diagnosingdementia. 

Biomarkers in Dementia 

Research 

Research on biomarkers for Alzheimer’s 

disease and other dementias has shown 

rapid progress. Biomarkers provide 

detailed measures of abnormal changes 

in the brain, which can aid in early 

detection of possible disease in people 

with very mild or unusual symptoms. 

People with Alzheimer’s disease and 

related dementias progress at different 

rates, and biomarkers may help predict 

and monitor their progression. 

In addition, biomarker measures may 

help researchers: 

n Better understand how risk factors 

and genetic variants are involved in 

Alzheimer’s disease 

n Identify participants who meet 

particular requirements, such as 

having certain genes or amyloid 

levels, for clinical trials and studies 

n Track study participants’ responses 

to a test drug or other intervention, 

such as physical exercise 

How You Can Help 

The use of biomarkers is allowing scientists to make great strides in identifying 

potential new treatments and ways to prevent or delay dementia. These advances 

are possible because thousands of people have participated in clinical trials and 

studies. Clinical trials need participants of all different ages, sexes, races, and 

ethnicities to ensure that study results apply to as many people as possible, and 

that treatments will be safe and effective for everyone who will use them. Major 

medical breakthroughs could not happen without the generosity of research 

participants who become partners in these scientific discoveries. 

To learn more about participating in clinical research, visit www.nia.nih.gov/health/

clinical-trials.

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The Future of Biomarkers 

Advances in biomarkers during the 

past decade have led to exciting new 

findings. Researchers can now see 

Alzheimer’s-related changes in the 

brain while people are alive, track the 

disease’s onset and progression, and 

test the effectiveness of promising 

drugs and other potential treatments. 

To build on these successes, researchers 

hope to further biomarker research by: 

n Developing and validating a full 

range of biomarkers, particularly 

those that are less expensive and/ 

or less invasive, to help test drugs 

that may prevent, treat, and improve 

diagnosis of Alzheimer’s and related 

dementias 

n Advancing the use of novel PET 

imaging, CSF, and blood biomarkers 

to identify specific changes in the 

brain related to Alzheimer’s and 

other neurodegenerative dementias 

n Using new MRI methods to measure 

brain structure, function, and 

connections 

n Developing and refining sensitive 

clinical and neuropsychological 

assessments to help detect and track 

early-stage disease 

n Using biomarkers in combination to 

build a model of Alzheimer’s disease 

progression over decades, from 

its earliest, presymptomatic stage 

through dementia 

For More Information 

Alzheimer’s and related Dementias 

Education and Referral (ADEAR) 

Center 

1-800-438-4380 (toll-free) 

adear@nia.nih.gov 

www.alzheimers.gov 

The National Institute on Aging’s 

ADEAR Center offers information and 

publications for families, caregivers, 

and professionals on diagnosis, 

treatment, patient care, caregiver 

needs, long-term care, education 

and training, and research related 

to Alzheimer’s disease and related 

dementias. Staff members answer 

telephone, email, and written requests 

and make referrals to local and national 

resources. Visit the ADEAR website 

to learn more about Alzheimer’s and 

related dementias, find clinical trials, 

and sign up for email updates. 

To find clinical trials and studies on 

Alzheimer’s and related dementias, visit: 

n ADEAR Center Clinical Trials Finder, 

www.nia.nih.gov/alzheimers/clinicaltrials 

n National Institute of Neurological 

Disorders and Stroke, www.ninds. 

nih.gov/disorders/clinical-trials 

n Alzheimer’s Disease Neuroimaging 

Initiative (ADNI), www.adni3.org 

n National Institutes of Health, 

www.ClinicalTrials.gov 

National Institute on Aging 

National Institutes of Health 

NIH...Turning Discovery Into Health® 

U.S. Department of Health and Human Services 

NIH Publication No. 18-AG-8044 8 June 2020