BIOMARKERS AND ALZHEIMER’S DISEASE

In those who meet the core clinical criteria, biomarker evidence may increase the certainty that Alzheimer’s disease (AD) is the underlying pathology.1

Biomarker confirmation of AD may improve disease care

Your patient's initial cognitive complaint or observed impairment may be your trigger to detect, assess, and diagnose early-stage AD. A key part of the process can be biomarker confirmation to support the diagnosis.1-4

The path to diagnosing early-stage AD1-6

Potential utility for biomarker confirmation

According to International Working Group (IWG) recommendations, a diagnosis of AD requires a clinical evaluation and confirmation of AD pathology. The diagnostic value of AD as the cause of MCI provides the clinician an opportunity to initiate patient care.7

Biomarkers focused on AD

There are a wide variety of biomarkers available for neuropathological diagnosis of AD. For instance, positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) tests can determine whether amyloid beta (Aβ) and tau pathology are present in the brain, biomarkers that are currently considered valid proxies for neuropathologic changes of AD.8

Many other biomarkers that are commonly used in research are non-specific indicators of neuronal damage. And while magnetic resonance imaging (MRI) is widely available and recommended as part of the diagnostic criteria, especially to rule out other possible causes, it lacks molecular specificity and cannot confirm AD pathology.9

Methods of evaluating biomarkers

PET Imaging

PET imaging uses radiotracers to bind to amyloid plaques or tau in the brain. The amyloid PET scan10:

  • Offers high diagnostic accuracy and localized information10
  • Provides a means to directly assess relative AD pathology in the brain10
  • May be used to establish biomarker relationships with changes in cognition and neurodegeneration11

Amyloid PET provides an image of Aβ aggregation8,12

Images from Huang CC, et al, used under CC BY 4.0, https://creativecommons.org
/licenses/by/4.0/.

CSF Test

Obtained via a lumbar puncture, a single collection of CSF can be used to assess brain pathology and to measure Aβ and tau biomarkers.8,10

  • Levels of Aβ in CSF are inversely related to the extent of cerebral Aβ deposits13
  • CSF phosphorylated tau (p-Tau) is a biomarker of the abnormal pathophysiology specifically associated with neurofibrillary tangles in AD. It is not elevated in primary tauopathies, head injury, or stroke8
  • CSF total tau is a biomarker of neuronal degeneration; it is not specific for AD8
  • Ratios of CSF biomarkers, eg, Aβ42/Aβ40 or p-Tau/Aβ42, are more accurate indicators of clinical AD and have less variability in assays than CSF Aβ42 alone14,15

CSF is collected between the 3rd and 4th, or 4th and 5th vertebrae15,16

INCREASE YOUR UNDERSTANDING OF BIOMARKERS WITH THIS Aβ TEST OVERVIEW

Studies have shown a strong correlation between CSF biomarkers and PET scan results.10

Care is responsive to a biomarker-confirmed diagnosis of AD

As the IDEAS Study has shown, accurate biomarker assessment increases the clinician’s confidence in AD diagnosis and allows for appropriate changes in management.17

The Alzheimer’s Care Locator

The Alzheimer’s Care Locator can help you find an Alzheimer’s specialist or diagnostic center for amyloid beta (Aβ) testing.

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What’s Next?

Early patient care in Alzheimer’s disease

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References

1.
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263-269.
2.
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270-279.
3.
Shaw LM, Arias J, Blennow K, et al. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers Dement. 2018;14(11):1505-1521.
4.
Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):e1-e16.
5.
Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561.
6.
Crous-Bou M, Minguillon C, Gramunt N, Molinuevo JL. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017;9(1):71. doi:10.1186/s13195-017-0297-z.
7.
Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. Lancet Neurol. 2021;20(6):484-496.
8.
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-562.
9.
Johnson KA, Fox NC, Sperling RA, Klunk WE. Brain imaging in Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(4):a006213. doi:10.1101/cshperspect.a006213.
10.
Porsteinsson AP, Isaacson RS, Knox S, Sabbagh MN, Rubino I. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis. 2021;8(3):371-386.
11.
Jack CR, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurology. 2013;12(2):207-216.
12.
Huang CC, Hsiao IT, Huang CY, et al. Tau PET with 18F-THK-5351 Taiwan patients with familial Alzheimer’s disease with the APP p.D678H mutation. Front Neurol. 2019;10:503. doi:10.3389/fneur.2019.00503.
13.
Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci. 2015;36(5):297-309.
14.
Lewczuk P, Matzen A, Blennow K, et al. Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis. 2017;55(2):813-822.
15.
Elecsys® β-Amyloid (1-42) CSF. Product information. Roche Diagnostics International Ltd; 2018.
16.
Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017;8:111-126.
17.
Rabinovici GD, Gatsonis C, Apgar C, et al. Association of amyloid positron emission tomography with subsequent change in clinical management among Medicare beneficiaries with mild cognitive impairment or dementia. JAMA. 2019;321(13):1286-1294.

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