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In conclusion, the effect of age on the plasma tau levels should always be considered in clinical applications of this surrogate biomarker to middle-aged and elderly subjects.

Diagnosis of preclinical Alzheimer’s disease (AD) or other suspected non-Alzheimer pathologies depends on the evidence of genetic carrier status and pathophysiological changes in the brain, such as shown by fluid and imaging biomarkers. Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: results of a pilot study. doi: 10.1016/j.resuscitation.20 Pub Med Abstract | Cross Ref Full Text | Google Scholar Sjögren, M., Vanderstichele, H., Agren, H., Zachrisson, O., Edsbagge, M., Wikkelso, C., et al. Tau and Aβ42 in cerebrospinal fluid from healthy adults 21–93 years of age: establishment of reference values.

The tau level in the CSF also correlates to severity of brain atrophy in the abovementioned natalizumab-treated multiple sclerosis patients at the 3-year follow-up (Mellergård et al., 2017).

The plasma tau levels of patients with neurological diseases have not been well studied until recently. doi: 10.1111/ene.13162 Pub Med Abstract | Cross Ref Full Text | Google Scholar Mortberg, E., Zetterberg, H., Nordmark, J., Blennow, K., Catry, C., Decraemer, H., et al. Plasma tau protein in comatose patients after cardiac arrest treated with therapeutic hypothermia.

However, no study has explored the effect of aging on the plasma tau protein level in normal population due to the even lower concentration of tau protein in the plasma of normal subjects. doi: 10.1016/20 Pub Med Abstract | Cross Ref Full Text | Google Scholar Mellergård, J., Tisell, A., Blystad, I., Grönqvist, A., Blennow, K., Olsson, B., et al. Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis.

The aims of the present study were to elucidate the effect of age on the plasma tau levels of cognitively normal middle-aged and older adults and to explore possible correlations between brain structures and the plasma tau protein levels in these cognitively normal subjects. 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.

The volunteers who participated in this study were asked to complete a medical checklist regarding major systemic diseases, operations and hospitalizations.

A study on Olympic boxers, who suffered from repetitive non-knocked-out head concussions from boxing bouts, plasma tau levels were elevated within 1–6 days of a bout and returned to normal after resting at least for a period of 14 days (Neselius et al., 2013). (2013) applied a single molecule array (Simoa) assay to quantitatively evaluate the total tau protein level in plasma and found that the plasma tau protein concentration of AD patients is higher than those of MCI patients and normal controls. (2013) assayed the plasma tau protein level using an immunomagnetic reduction assay and showed that the levels of plasma tau protein are higher in patients with MCI due to AD and in patients with AD dementia than in normal controls. Acute traumatic brain injury may also cause increased release of tau protein into the CSF (Zemlan et al., 1999). doi: 10.3109/02699052.2012.750752 Pub Med Abstract | Cross Ref Full Text | Google Scholar Otto, M., Wiltfang, J., Tumani, H., Zerr, I., Lantsch, M., Kornhuber, J., et al. Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. The tau level in the CSF has been associated with hippocampal atrophy in some studies (Hampel et al., 2005; Desikan et al., 2011; de Souza et al., 2012). doi: 10.1111/j.1399-6576.2011.02505.x Pub Med Abstract | Cross Ref Full Text | Google Scholar Neselius, S., Zetterberg, H., Blennow, K., Randall, J., Wilson, D., Marcusson, J., et al. Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma. Patients with AD were reported to have three-fold higher CSF tau levels (Hampel et al., 2008); some considered it is a potential biomarker of AD (Lewczuk et al., 2017); and even might predict a rapid progression from mild cognitive impairment (MCI) to AD-associated dementia (van Rossum et al., 2012). doi: 10.1016/S0304-3940(97)00215-2 Pub Med Abstract | Cross Ref Full Text | Google Scholar Randall, J., Mörtberg, E., Provuncher, G. However, in addition to patients with AD, increased total tau levels in the CSF of patients with certain other neurological diseases, such as acute stroke, Creutzfeldt-Jakob disease and natalizumab-treated multiple sclerosis (Otto et al., 1997; Hesse et al., 2000; Kapaki et al., 2001; Llorens et al., 2016; Mellergård et al., 2017).

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