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P3‐003: Cerebrospinal fluid amyloid beta 40 and the amyloid beta 42/40 ratio in differentiating Alzheimer's disease from other dementias
Author(s) -
Spies Petra,
Slats Diane,
Sjögren Magnus,
Kremer Berry,
Verhey Frans,
Rikkert Marcel Olde,
Verbeek Marcel
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.1180
Subject(s) - dementia with lewy bodies , cerebrospinal fluid , dementia , alzheimer's disease , vascular dementia , medicine , frontotemporal dementia , amyloid beta , differential diagnosis , amyloid (mycology) , beta (programming language) , gastroenterology , pathology , central nervous system disease , disease , endocrinology , computer science , programming language
Background: CSF biomarkers amyloid beta 1-42 (Ab42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) are useful diagnostic markers for Alzheimer’s disease (AD). Less is known about these biomarkers as predictors for further cognitive decline in patients with AD. We hypothesized that high tau, especially in combination with relatively low ptau-181, is a marker of rapid decline, since it has been associated with fast neuronal degeneration. Methods: 151 AD patients, of whom we had baseline CSF, were included from our memory clinic. All patients had at least 2 Mini Mental Status Examination (MMSE) scores, no less than one year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles. Random intercept and random slope with time were assumed and the analyses were corrected for sex and age. Results: The AD patients (45%F, 6669years, baseline MMSE 2264) had a follow-up period of 2.361.1years (mean6SD). Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low ptau-181/tau-ratio was the strongest predictor with a dose dependent effect (p for trend <0.005). A low ptau-181/tau-ratio predicted twice faster annual cognitive decline; patients with a ptau-181/tau ratio in the lowest quintile deteriorated 2.960.56 MMSE-points/year, while those in the highest quintile deteriorated only 1.260.43 points/year (b6SE). In addition, low Ab42, high tau and high tau/Ab42-ratio were associated with more rapid cognitive decline (p for trend <0.05). Conclusions: Patients with high rates of neuronal damage, as reflected by higher CSF tau, especially in combination with a relatively low phosphorylation rate, as reflected by less elevated CSF ptau-181, have the most aggressive type of AD. This observation could be helpful in unravelling the pathophysiology in AD. Furthermore, our results show that in addition to diagnostic value CSF biomarkers also have prognostic value. Patients with disproportionally elevated tau levels compared to ptau-181 levels are prone to fast cognitive decline, while patients with less extreme tau levels compared to ptau-181 are expected to be relatively stable.