1st order laboratory parameters – obligatory laboratory tests.
- Evidence for Alzheimer’s disease pathology by at least one of the following:
- Positive amyloid detection with positron emission tomography (PET) (see table below).
- Genetic testing (DNA analysis): mutation leading to monogenic-mediated Alzheimer’s disease (mutation on the presenilin 1 or presenilin 2 genes or on the gene of the amyloid precursor protein, APP).
- CSF diagnostics (recognized dementia biomarkers are amlyoid-β1-42 (Aβ1-42), amlyoid-β1-40 (Aβ1-40), total tau and phospho-tau-181 (pTau), and 14-3-3 protein) [decreased Aß42 in CSF and increased tau protein or phosphorylated tau protein in CSF].
- Beta-amyloid precursor protein (APP) in serum; quotient of APP 669-711 to amyloid-beta 1-42 and also the quotient of Abeta 1-40 to Abeta 1-42; diagnostic accuracy: about 90% (not yet routine diagnostics).
- Amyloid-β folding: detection of defective folding of the protein amyloid-β in the blood; this occurs as early as 15 to 20 years before the onset of the first symptoms.Amyloid determination showed an up to 23-fold increased risk of disease compared with the control group; in contrast, APOE4 status showed only a 2.4-fold increased risk. Note: A pathological finding of the analysis of amyloid beta vera.
- Tau proteins (determination by “single molecule array”; detection limit of tau proteins was lowered to 0.019 pg/ml) – detection of impending dementia and related disorders already 4 years before the first symptoms (not yet routine diagnostics).
- Small blood count [MCV ↑ → possible evidence of alcohol dependence, vitamin B12 and folic acid deficiency]
- Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
- Electrolytes – sodium, potassium calcium.
- Fasting glucose (fasting plasma glucose; preprandial plasma glucose; venous), oral glucose tolerance test (oGTT) if necessary.
- Liver parameters – aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), gamma-glutamyl transferase (γ-GT, gamma-GT; GGT) [γ-GT ↑, possible indication of alcohol dependence].
- Renal parameters – urea, creatinine, possibly cystatin C or creatinine clearance.
- TSH (thyroid-stimulating hormone) – to exclude hypo- or hyperthyroidism (hypothyroidism or hyperthyroidism).
- Vitamin B12
Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification.
- Differential blood picture
- Blood gases (ABG), arterial
- Drug screening including narcotics (alcohol, barbiturates, benzodiazepines, bromides).
- Lues serology: VDRL test (for V. d. on neurolues).
- HIV serology
- Borrelia serology
- Phosphate
- HbA1c
- Homocysteine
- FT 3, fT4, SD antibodies – to rule out hypothyroidism (especially Hashimoto’s thyroiditis), this can lead to rapidly progressive dementia
- Cortisol
- Parathyroid hormone – to exclude hypo- or hyperparathyroidism (parathyroid hypo- or hyperfunction).
- Coeruloplasmin
- Serum albumin
- Ammonia level
- Folic acid, vitamin B1, B6
- Copper
- Heavy metals (arsenic, lead, mercury, thallium).
- CO hemoglobin
- Carbodeficient transferrin (CDT) ↑ (in chronic alcoholism)* .
- Histopathology: major components of pathologic neurofibrillary tangles and senile plaques are a hyperphosphorylated form of P-Tau181 protein and ß-amyloid 1-42
Probable or possible dementia in Alzheimer’s disease with clues to the pathophysiological process of Alzheimer’s disease:
| Amyloid marker | Neuronal damage marker |
| Decrease of Aβ42 in cerebrospinal fluid. | Increase of tau and/or of phosphorylated tau in the CSF |
| Amyloid detection by positron emission tomography (PET). | Atrophy of the medial temporal lobe-imaged by magnetic resonance imaging (MRI). |
| Parietotemporal hypometabolism-imaged by fluorodeoxyglucose positron emission tomography (FDG-PET). |
Biomarkers for the diagnosis of Alzheimer’s disease
A committee assembled by the National Institute on Aging (NIA) and the Alzheimer’s Association (AA) in “Alzheimer’s and Dementia” is turning away from symptomatology and wants to use biomarkers for the diagnosis of Alzheimer’s disease (AD) as decisive criteria in future research (see below Laboratory Diagnostics).
| AT (N) biomarker groups. | |
| A | Aß detected as plaques in PET scan or as Aβ42 or Aβ42/Aβ42 ratio in CSF. |
| T | Tau pathology as p-tau (phosphorylated tau) in cerebrospinal fluid or as parenchymal neurofibrils on PET scan |
| (N) | Signs of neurodegeneration on structural MRI or FDG PET or as T(otales)-tau in CSF. |
Note: A and T are considered to be specific for Alzheimer’s disease, (N) is not. This results in the following AT (N) profiles.
| Result | Assessment |
| All biomarkers in the normal range (A-T-(N)-) | No Alzheimer’s disease |
| A+ only | Pathological Alzheimer’s changes, but no Alzheimer’s disease yet. |
| A+T+(N)- or A+T+(N)+ | Alzheimer’s disease criteria met |
| A+T-(N)+ | Alzheimer’s changes (non-Alzheimer’s disease) and non-specific neurodegeneration. |
| A-T+(N)- or A-T-(N)+ or A-T+(N)+ | No Alzheimer’s changes, no Alzheimer’s disease, non-Alzheimer’s changes. |
Prediction of Alzheimer’s disease based on a multimodal risk score.
- Prediction of dementia risk in older people with mild cognitive impairment (MCI) based on a multimodal risk score using CSF levels of beta-amyloid and tau and normalized total brain volume:
- Here, little beta-amyloid in the CSF means that much is clumped in the brain
- High beta-amyloid levels (around 1,100 pg/ml) and low tau levels (below 500 pg/ml) in CSF with low brain atrophy (1600 ml brain volume): three-year risk of dementia close to 0 percent
- Moderately high beta-amyloid and tau levels in CSF in the presence of marked brain atrophy (1,200 ml total brain volume)): Three-year risk of dementia almost 100 percent
- Low beta-amyloid levels (200 pg/ml) and high tau levels (900 pg/ml) in the CSF in the presence of mild brain atrophy: three-year risk for dementia almost 100 percent
