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Updated: Nov 19, 2025
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer's disease
Maurits Johansson1,2,3, Erik Stomrud4,5, Philip S Insel4,6
1Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, SUS, Malmö, Sweden. maurits.johansson@med.lu.se.
Abstract:
Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer's disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([18F]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau181. Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau181 levels were associated with higher MBI-C scores (β = 0.010, SE = 0.003, p = 0.003 and β = 1.263, SE = 0.446, p = 0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (β = 0.009, p = 0.009) and CSF P-tau181 (β = 0.408, p = 0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.
Insights
Mild behavioral impairment (MBI) is linked to tau pathology in preclinical Alzheimer's disease, independent of memory decline. This suggests MBI may be an early indicator of AD-related tau changes.
Area of Science:
- Neuroscience
- Neurology
- Biomarkers
Background:
- Mild behavioral impairment (MBI) is a potential risk marker for neurodegenerative diseases like Alzheimer's disease (AD).
- Pathologic tau deposition is closely linked to clinical manifestations in AD, but its association with MBI is under-investigated.
- The temporal relationship between MBI and cognitive deficits in AD remains debated.
Purpose of the Study:
- To explore the relationship between MBI and tau pathology in preclinical AD.
- To investigate if MBI precedes cognitive deficits in the context of AD.
- To examine potential mechanisms linking MBI to AD through tau pathology.
Main Methods:
- Studied 50 amyloid-β-positive, cognitively unimpaired subjects from the BioFINDER-2 study.
- Assessed MBI using the Mild Behavioral Impairment Checklist (MBI-C).
- Measured episodic memory with the Alzheimer's Disease Assessment Scale - Cognitive subscale delayed word recall (ADAS-DR).
- Determined early tau pathology via tau-PET ([18F]RO948) in the entorhinal cortex/hippocampus and cerebrospinal fluid (CSF) P-tau181 levels.
- Employed regression models to analyze associations between MBI, tau markers, and cognitive function.
Main Results:
- Higher tau-PET signal and CSF P-tau181 levels were significantly associated with higher MBI-C scores.
- MBI-C scores predicted tau-PET and CSF P-tau181 levels when analyzed alongside ADAS-DR.
- ADAS-DR (episodic memory) was not predicted by MBI-C in the presence of tau markers.
Conclusions:
- In preclinical AD, MBI is associated with tau pathology independently of memory deficits.
- MBI represents a significant early clinical manifestation linked to tau pathology in AD.
- These findings highlight MBI as a crucial early indicator in the AD continuum.
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