Introduction
The Alzheimer continuum: a new concept that has an impact on diagnosis, prevention, and treatment strategies
The diagnosis of Alzheimer’s disease relies on different biomarker categories: amyloid-Β deposition, neurofibrillary tangles, and neuronal degeneration
Pathological change | Biomarker category | Biomarker(s) |
---|---|---|
Aβ deposition = early marker
| Biochemical (CSF) Molecular imaging | CSF Aβ1-42 or Aβ1-42/Aβ1-40
PET with amyloid-specific probes |
NFT formation | Biochemical (CSF) | CSF P-tau181
|
Neuronal injury = downstream
| Biochemical (CSF) Topographical | CSF T-tau [18F]FDG-PET SPECT HCV / MTL atrophy on MRI |
Combining biomarkers to increase diagnostic accuracy
Diagnostic accuracy is independent from the analytical platform
The Alzheimer’s disease cerebrospinal fluid biomarker panel
Standardization and harmonization efforts
Contributions and relevance of standardization and harmonization efforts
Clinical indications for using the Alzheimer’s disease cerebrospinal fluid biomarker panel
To increase the diagnostic accuracy in case of suspected Alzheimer’s disease
To diagnose Alzheimer’s disease in its earliest stages
Pre-clinical Alzheimer’s disease
Prodromal Alzheimer’s disease
To discriminate Alzheimer’s disease from other neurodegenerative and cerebrovascular brain disorders: differential diagnosis
To identify Alzheimer’s disease in case of suspected mixed brain pathologies
To diagnose Alzheimer’s disease in case of a typical presentations
Future cerebrospinal fluid biomarkers for Alzheimer’s disease (differential) diagnosis
New biomarkers for differential dementia diagnosis
Cerebospinal fluid biomarkers that predict Alzheimer’s disease progression
Discussion
Early diagnosis or timely diagnosis?
Evidence-based clinical indications for application of the Alzheimer’s cerebrospinal fluid biomarker panel
Conclusions (Table 2)
Perform CSF analysis | New CSF biomarkers | |
---|---|---|
Suspected AD diagnosis | ||
Early-onset dementia | Yes | |
No doubt in clinical diagnosis | No | |
Ambiguous clinical diagnosis | Yes | |
Early AD diagnosis | ||
Pre-clinical AD | ||
Clinical research | Yes | |
Cognitively healthy elderly | No | |
Prodromal AD | ||
Clinical evidence for cognitive decline | Yes | |
Differential dementia diagnosis (AD versus non-AD dementia) | Yes | Aβ1-42/Aβ1-40, t-PrP, Aβ1-37, Aβ1-38, α-synuclein |
Mixed dementia pathology diagnosis | ||
AD as co-pathology | No | |
AD versus AD–CVD | Yes | |
Atypical AD diagnosis | ||
Diagnose atypical AD variants | Yes |