Abstract
Alzheimer’s
disease (AD) is the most common neurodegenerative disease and its
diagnosis has classically been based on clinical symptoms. Recently, a
biological rather than a syndromic definition of the disease has been
proposed that is based on biomarkers that reflect neuropathological
changes. In AD, there are two main biomarker categories, namely
neuroimaging and fluid biomarkers [cerebrospinal fluid (CSF) and blood].
As a complex and multifactorial disease, AD biomarkers are important
for an accurate diagnosis and to stage the disease, assess the
prognosis, test target engagement, and measure the response to
treatment. In addition, biomarkers provide us with information that,
even if it does not have a current clinical use, helps us to understand
the mechanisms of the disease. In addition to the pathological hallmarks
of AD, which include amyloid-β and tau deposition, there are multiple
concomitant pathological events that play a key role in the disease.
These include, but are not limited to, neurodegeneration, inflammation,
vascular dysregulation or synaptic dysfunction. In addition, AD patients
often have an accumulation of other proteins including α-synuclein and
TDP-43, which may have a pathogenic effect on AD. In combination, there
is a need to have biomarkers that reflect different aspects of AD
pathogenesis and this will be important in the future to establish what
are the most suitable applications for each of these AD-related
biomarkers. It is unclear whether sex, gender, or both have an effect on
the causes of AD. There may be differences in fluid biomarkers due to
sex but this issue has often been neglected and warrants further
research. In this review, we summarize the current state of the
principal AD fluid biomarkers and discuss the effect of sex on these
biomarkers.
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