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The Study

Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

In simple terms

This study watched people over time and saw that when the brain starts making too much amyloid (a sticky protein), it also starts changing another protein called tau in the fluid around the brain — but the bad tau clumps don’t show up on scans until years later. It’s like seeing smoke before the fire starts, but we can’t say the smoke caused the fire — just that they often happen together.

54%

Analysis score

54/ 72

Maximum 72 for a cohort study.

Where the score came from

Reporting0
Methodology43
Publication100
Statistical77
Study type (basis of the score)
Cohort Study
Level 2b - Individual cohort study
What’s the bottom line?

Before the brain forms sticky tau tangles, a soluble form of tau in spinal fluid starts rising — but only if amyloid plaques are already present.

Where does this study sit?

Reviews of RCTs (Meta-analyses)

Max 100

Randomized Trials

Max 90

Reviews of Cohort Studies

Max 85

Cohort Studies

Max 72

Reviews of Case-Control Studies

Max 63

Case-Control Studies

Max 58

Cross-Sectional & Case Series

Max 50

Expert Opinion

Max 5
StrongerWeaker
Cohort Studies
Level 2b
54

54 / 100

Quality score

Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.

Cannot establish causation

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Key takeaways

Summary

Based on the study abstract and findings.

  1. 1This means doctors could detect Alzheimer’s risk years earlier by testing spinal fluid for P-tau217 — before memory problems or brain scans show damage.
  2. 2P-tau217 rises 12 years before tau tangles show up on PET scans; it increases even before amyloid PET is officially positive; 70% of people with amyloid plaques have high P-tau217 before tau PET turns positive.

Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data

Publication

Journal

Science Advances

Year

2020

Authors

N. Mattsson‐Carlgren, E. Andersson, S. Janelidze, R. Ossenkoppele, P. Insel, O. Strandberg, H. Zetterberg, H. Rosen, G. Rabinovici, Xiyun Chai, K. Blennow, Jeffrey L. Dage, E. Stomrud, Ruben Smith, S. Palmqvist, O. Hansson

Open Access
303 citations
Analysis v6

Related Content

Claims (6)

Assertion

Phosphorylated tau protein can be detected in the brain using neuroimaging techniques 12 years before a person shows any signs of Alzheimer's disease.

Descriptive
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Assertion

Levels of phosphorylated tau proteins in cerebrospinal fluid account for 68–82% of the connection between amyloid-beta buildup and the formation of neurofibrillary tangles in the brain.

Mechanistic
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Assertion

In people with early Alzheimer's-related brain changes but no cognitive symptoms, phosphorylated tau proteins in spinal fluid rise before tau clumps become visible on brain scans, with phosphorylated tau-217 increasing first and most strongly.

Mechanistic
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Assertion

In people with early amyloid buildup in the brain, a specific form of tau protein called P-tau217 increases in cerebrospinal fluid before amyloid PET scans show abnormal levels.

Descriptive
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Assertion

People with a genetic mutation that causes tau protein to clump in the brain but who do not have amyloid-beta plaques have normal levels of phosphorylated tau in their spinal fluid, showing that this specific tau modification requires amyloid-beta to occur.

Mechanistic
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Assertion

In genetically modified mice that develop amyloid plaques but not tau tangles, levels of soluble tau in the cerebrospinal fluid rise as amyloid-beta accumulates, showing that amyloid pathology can trigger soluble tau release without the presence of tau aggregates.

Mechanistic
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