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Updated: May 10, 2025
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Association between high plasma p-tau181 level and gait changes in patients with mild cognitive impairment
Chenglu Mao1,2,3,4, Yuting Mo5,6,7,8, Jialiu Jiang9,6,7,8
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210000, China. maochenglu922@gmail.com.
Abstract:
Previous studies on gait changes in mild cognitive impairment (MCI) are inconsistent. Alzheimer's disease (AD) plasma biomarkers, amyloid beta (Aβ) and phosphorylated-tau (p-tau), are relevant to gait disorders. This study explores gait changes in MCI and the relationship between gait performance and AD plasma biomarkers. 231 participants were recruited and stratified based on p-tau181 levels into: low p-tau181 with normal cognition (lT-NC), low p-tau181 with MCI (lT-MCI), and high p-tau181 with MCI (hT-MCI). The same cohort was subsequently stratified by Aβ42/Aβ40 levels into: high Aβ42/Aβ40 with normal cognition (hA-NC), high Aβ42/Aβ40 with MCI (hA-MCI), and low Aβ42/Aβ40 with MCI (lA-MCI). Demographic, cognitive and gait data were compared across groups. The hT-MCI and lA-MCI groups were older than the other groups. Significant differences in stride length were found between lT-NC and hT-MCI, lT-MCI and hT-MCI, but not between lT-NC and lT-MCI. Neuropsychological assessments revealed poorer performance in hT-MCI and lT-MCI groups relative to lT-NC, while global cognitive function was comparable between hT-MCI and lT-MCI groups. No such associations were observed between stride length and Aβ42/Aβ40 levels. Decreased stride length, which is generally considered to be indicative of poorer gait, was significantly associated with elevated p-tau181 levels and independent of global cognitive status. These findings highlight the potential of p-tau181 as a biomarker for tau-related motor dysfunction in MCI.
Insights
Elevated phosphorylated-tau (p-tau) levels, not amyloid beta, are linked to reduced stride length in mild cognitive impairment (MCI). This suggests p-tau may indicate motor dysfunction in MCI patients.
Area of Science:
- Neuroscience
- Gerontology
- Biomarker Research
Background:
- Gait disturbances are increasingly recognized in mild cognitive impairment (MCI), but previous research findings are inconsistent.
- Alzheimer's disease (AD) plasma biomarkers, including amyloid beta (Aβ) and phosphorylated-tau (p-tau), are implicated in neurological disorders and may relate to gait impairments.
Purpose of the Study:
- To investigate gait changes in individuals with MCI.
- To explore the relationship between gait performance and AD plasma biomarkers, specifically p-tau181 and Aβ42/Aβ40 ratio.
- To determine if gait alterations in MCI are associated with specific AD pathological markers.
Main Methods:
- 231 participants were recruited and categorized into groups based on cognitive status (normal cognition vs. MCI) and plasma p-tau181 levels (low vs. high).
- The cohort was further stratified by plasma Aβ42/Aβ40 levels (high vs. low).
- Gait parameters (e.g., stride length) and cognitive function were assessed and compared across these distinct groups.
Main Results:
- Decreased stride length, a marker of poorer gait, was significantly associated with elevated p-tau181 levels in MCI participants.
- This association between reduced stride length and high p-tau181 remained significant and was independent of global cognitive status.
- No significant association was found between stride length and Aβ42/Aβ40 levels in the studied cohort.
Conclusions:
- Elevated plasma p-tau181 levels are linked to reduced stride length in individuals with mild cognitive impairment.
- p-tau181 may serve as a valuable biomarker for detecting tau-related motor dysfunction in the context of MCI.
- Gait performance, particularly stride length, shows a stronger association with tau pathology than amyloid pathology in MCI.
