Cerebrospinal Fluid Biomarkers are Differentially Related to Structural and Functional Changes in Dementia of the Alzheimer's Type

The two cardinal pathologies of Alzheimer's disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer's type. Interrelationships were analyzed between cerebrospinal fluid biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [F-18]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Alzheimer's disease
amyloid-beta
cerebral glucose uptake
cerebrospinal fluid
cortical thickness
P-
mild cognitive impairment
default-mode network
amyloid deposition
csf
biomarkers
tau-protein
disease
brain
beta
atrophy
pet
Neurosciences & Neurology

Saling, M. M. (author)
Velakoulis, D. (author)
Desmond, P. (author)
Hicks, R. J. (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
O'Brien, T. J. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

By the author/editor: Malpas, C. B.; Saling, M. M.; Velakoulis, D.; Desmond, P.; Hicks, R. J.; Zetterberg, Henr ...; show more...; Blennow, Kaj, 19 ...; O'Brien, T. J.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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