Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

January 13, 2022

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Background:

What Happens to the Brain in Alzheimer's Disease?

• What Are the Main Characteristics of the Brain with Alzheimer’s?

Many molecular and cellular changes take place in the brain of a person with Alzheimer’s disease. These changes can be observed in brain tissue under the microscope after death. Investigations are underway to determine which changes may cause Alzheimer’s and which may be a result of the disease.

Amyloid Plaques

The beta-amyloid protein involved in Alzheimer’s comes in several different molecular forms that collect between neurons. It is formed from the breakdown of a larger protein, called amyloid precursor protein. One form, beta-amyloid 42, is thought to be especially toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function. Research is ongoing to better understand how, and at what stage of the disease, the various forms of beta-amyloid influence Alzheimer’s.

Neurofibrillary Tangles

Neurofibrillary tangles are abnormal accumulations of a protein called tau that collect inside neurons. Healthy neurons, in part, are supported internally by structures called microtubules, which help guide nutrients and molecules from the cell body to the axon and dendrites. In healthy neurons, tau normally binds to and stabilizes microtubules. In Alzheimer’s disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.

Emerging evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and beta-amyloid proteins and several other factors. It appears that abnormal tau accumulates in specific brain regions involved in memory. Beta-amyloid clumps into plaques between neurons. As the level of beta-amyloid reaches a tipping point, there is a rapid spread of tau throughout the brain.

Chronic Inflammation

Research suggests that chronic inflammation may be caused by the buildup of glial cells normally meant to help keep the brain free of debris. One type of glial cell, microglia, engulfs and destroys waste and toxins in a healthy brain. In Alzheimer’s, microglia fail to clear away waste, debris, and protein collections, including beta-amyloid plaques. Researchers are trying to find out why microglia fail to perform this vital function in Alzheimer’s.

Full article:

https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

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Abstract

Introduction

Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers.

Methods

Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161).

Results

Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD.

Discussion

Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

"Furthermore, we found that levels of NfL, GFAP, and UCHL1 were as high as, or significantly higher than, those observed in non-COVID patients with AD, indicating a profound neurological insult in these patients."

5 CONCLUSIONS

Serum neuronal, glial, and axonal neurodegenerative biomarkers, including t-tau, p-tau181, UCHL1, GFAP, and NfL were significantly elevated in patients with encephalopathy and worse discharge disposition after hospitalization for COVID-19. These markers correlated with the severity of COVID illness. Furthermore, levels of NfL, GFAP, and UCHL1 in hospitalized COVID patients were similar to, or higher than, levels observed in non-COVID AD dementia patients. Additional studies tracking trajectories of these biomarkers over time and their association with long-term cognitive outcomes among COVID-19 survivors are warranted.

Full paper:

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12556