One study evaluated the ability of EEG alone or with resting state functional MRI (rsfMRI) to characterise mild cognitive impairment (MCI) subjects with an AD-like cerebrospinal fluid (CSF) biomarker profile [1]. A total of 39 AD, 86 MCI, and 86 healthy subjects underwent EEG and/or rsfMRI. MCI subjects were differentiated into phosphorylated tau/Aβ1-42 ratio ≥0.13 (MCI-ATpos) and <0.13 (MCI-ATneg). In AD patients, delta and theta densities were increased, and alpha2 and beta1 densities decreased. MCI-ATpos individuals had higher theta density than MCI-ATneg individuals. After the application of rsfMRI networks to current source density analysis, the alpha2 band could distinguish MCI-ATpos patients from MCI-ATneg, AD, and healthy individuals. The authors concluded that theta frequency was the most sensitive to AD-like CSF biomarker profile. These results emphasise the role of the alpha2 band as a biomarker for neurodegeneration correlating with disease progression.
A new biomarker that could reflect beta-secretase 1 (BACE1) activity and cognitive alteration in AD patients is Neuregulin1 (Nrg1). Nrg1 is a presynaptic BACE1 substrate that can activate postsynaptic ErbB4 receptors. Neuritic plaques are associated with Nrg1 accumulation in AD [2]. CSF Nrg1 levels were evaluated in 172 individuals: 56 had AD, 21 MCI-AD, 32 non-AD MCI, and 36 non-AD dementia; the other 27 were neurological controls [3]. In AD and MCI-AD patients, CSF Nrg1 concentrations were significantly enhanced. Nrg1 levels correlated positively with tau, phosphorylated tau, Aβ1-40, and BACE1 levels, and negatively with Mini-Mental State Examination (MMSE) scores and frontal battery scores. The authors concluded that Aβ-induced neurotoxicity induced synaptic demise with increased CSF BACE1 and Nrg1 levels. They postulate that lack of neuroprotection may be linked to decreased Nrg1 brain levels.
New research supports the systematic use of the concentration ratio of Aβ1-42 to Aβ1-40 (Aβ1-42/1-40 ratio) as an amyloid biomarker in diagnosing AD [4]. A French group found significant differences in amyloid status according to the ATN system (A+/A-) in CSF between absolute values of Aβ1-42 and of Aβ1-42/1-40 ratio. The modification of the amyloid status (A- or A+) after Aβ1-42/1-40 ratio calculation was analysed in CSF of 738 subjects with a mean age of 69 years. Of patients deemed A+ after Aβ1-42 measurement, 67% became A- after Aβ1-42/1-40 ratio calculation (P<0.0001), while 18% of A- subjects became A+ (P<0.0001). These findings confirm the recent suggestion that the Aβ1-42/1-40 ratio may be more specific to distinguish AD and should be used when analysing CSF AD biomarkers [5].
- Agosta F, et al. EPR1001, EAN 2020.
- Chaudhury AR, et al. J. Neuropathol. Exp. Neurol. 2003;62(1):42-54.
- Mouton Liger F, et al. EPR2004, EAN 2020.
- Tisserand C, et al. EPR2009, EAN 2020.
- Hansson O, et al. Alzheimers Res Ther. 2019;11(1):34.
Posted on
Previous Article
« Diastolic dysfunction novel risk factor for cognitive impairment Next Article
Novel genetic association with resistance to ERC tau deposition »
« Diastolic dysfunction novel risk factor for cognitive impairment Next Article
Novel genetic association with resistance to ERC tau deposition »
Table of Contents: EAN 2020
Featured articles
Alzheimer's Disease and Other Dementias
Non-Alzheimer’s disease pathophysiology in the elderly
Novel genetic association with resistance to ERC tau deposition
Diastolic dysfunction novel risk factor for cognitive impairment
Epilepsy
Avoidable epilepsy-related mortality remains high
How genetic testing can contribute to epilepsy management
Cenobamate effective in focal epilepsy
Sustained seizure reductions with cannabidiol for Lennox-Gastaut syndrome
Prevalence of autoantibodies in epilepsy almost 10%
Parkinson's Disease
White matter matters in Parkinson’s disease
Sleep disorders mark PD progression
Directional DBS superior to omnidirectional DBS
Stroke
Benefits of statins to prevent stroke outweigh risks
Extubation after thrombectomy: the sooner, the better
Thrombus location and length predictors of early neurological deterioration
Endovascular treatment in large vessel occlusion stroke patients treated with OAC
Early edoxaban may be safe after cardioembolic stroke
Headache and Pain
Small fibre pathology as biomarker for fibromyalgia
Migraine as a cyclical functional disorder
Reassuring real-world safety profile of 3 CGRP inhibitors
Long-term cardiovascular safety of erenumab
Real-world data for erenumab in Germany
Eptinezumab in chronic migraine and medication-overuse headache
Fremanezumab tolerability in cardiovascular patients with migraine
Effects of galcanezumab on health-related quality of life
Multiple Sclerosis
Imaging to evaluate remyelination and neuroprotection
Serum NfL predicts long-term clinical outcomes in MS
Epstein-Barr virus-targeted T-cell immunotherapy for progressive MS
High NEDA rates after 2 years of ocrelizumab
Switching from natalizumab to moderate- versus high-efficacy DMT
Results of compounds in late stages of development
Alemtuzumab efficacy and safety data of over 9 years
Fampridine treatment results in routine clinical practice
Air pollution is a possible risk factor for MS
Neuromyelitis Optica Spectrum Disorder
Genetic association studies in NMOSD needed
Eculizumab in NMOSD: the PREVENT study
Long-term safety of satralizumab consistent with double-blind periods
Neuromuscular Disorders
Biomarkers predicting motor function in SMA
Sustained benefits of avalglucosidase alfa in late-onset Pompe disease
Efficacy and safety of rituximab in refractory MG corroborated
Related Articles

September 9, 2020
Cenobamate effective in focal epilepsy
September 9, 2020
Fremanezumab tolerability in cardiovascular patients with migraine
September 9, 2020
Benefits of statins to prevent stroke outweigh risks
© 2023 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy