Diagnosis of AD
The initial manifestations of Alzheimer’s Disease (AD) frequently
encompass cognitive domains beyond memory, encompassing challenges in
lexical retrieval, visual processing, spatial orientation, compromised
reasoning abilities, and impaired judgment. Memory deficits represent a
salient and discernible manifestation of Alzheimer’s
disease1.
In the realm of dementia diagnosis, encompassing Alzheimer’s disease
(AD) as well, a multitude of imaging techniques are
employed6,7. The utilization of CT scans facilitates
the examination of alterations in the dimensions of cerebral regions,
which are subsequently juxtaposed with either prior scans or projected
cerebral sizes corresponding to individuals of commensurate age and
physique. Magnetic Resonance Imaging (MRI) plays a pivotal role in the
identification and characterization of anomalous cerebral alterations,
notably brain atrophy. Fluorodeoxyglucose positron emission tomography
(FDG-PET) scans are employed to quantify glucose uptake within the
cerebral region, exhibiting diminished levels in specific regions among
individuals afflicted with dementia. Consequently, these scans have
proven to be valuable tools for diagnostic endeavors. The utilization of
amyloid positron emission tomography (PET) scans enables the
identification and quantification of anomalous accumulations of
beta-amyloid protein, a distinctive characteristic associated with
Alzheimer’s disease (AD). The utilization of amyloid PET scans in
clinical practice often involves the administration of various tracers,
such as florbetapir, flutemetamol, florbetaben, and Pittsburgh compound
B. Tau positron emission tomography (PET) scans, which employ tracers
such as AV-1451, PI-2620, and MK-6240, have demonstrated their efficacy
in identifying pathological tau protein aggregates, thereby serving as a
valuable tool for monitoring the progression of Alzheimer’s disease (AD)6,7.
Lumbar punctures are commonly utilized in the identification of
cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD),
including beta-amyloid 42, tau, and phospho-tau6,7.
Blood tests represent an additional modality for the diagnosis of
Alzheimer’s disease (AD), with the primary objective of detecting
brain-derived biomarker proteins such as beta-amyloid 42/beta-amyloid 40
and phospho-tau 181. The present diagnostic methods for Alzheimer’s
disease (AD) exhibit a degree of predictability; however, their
sensitivity and accuracy may be enhanced to enable more precise and
early detection of AD. This can be achieved through the integration of
advanced technologies, such as nanoparticles, with existing imaging
agents and tracers. The aforementioned advancements possess the
potential to expedite the initiation of therapeutic interventions,
thereby potentially impeding the progression of the disease and
mitigating the symptoms associated with Alzheimer’s disease (AD)6,7.
Recent studies have been focused on developing integrative methods with
nanoparticles to enhance current diagnostic procedures. One study by
Razzino et al., synthesized gold-polyamidoamine dendrimer nanocomposites
conjugated with screen-printed carbon electrodes (SPCE) to facilitate
enhanced diagnosis of AD. The nanocomposites were also functionalized
with anti-tau antibodies, allowing tau tangles to aid as the target for
diagnosis of AD. In the study by Kim et al., long gold-nanoparticle
based nanorods were found to detect tau levels at a significantly low
dose of 23.6 fM. One limitation of tau-targeting gold-nanoparticle
biosensors is the difficulty of the tau epitopes to be accessible to the
biosensor. The hydrophobic bonds between tau proteins and the hydrogen
bonding between tau epitopes often limit the ability of
nanoparticle-based biosensors to detect the tau protein. This challenge
can be overcome by coupling the nanoparticle-based biosensor with
chaotropic agents to hinder tau-tau interactions. With this, the
nanoparticles-based biosensors were able to detect significantly low tau
concentrations of 0.1 pM, compared to the 1.0 pM tau concentration
detected by the nanoparticle-based biosensor without the chaotropic
agents. Although these studies have found success in implementing gold
nanoparticles as in vitro biosensing platforms, further research
is necessary to establish their biocompatibility, administration, and
bioaccumulation in vivo. Another recent study fabricated magnetic
nanoparticles coated with dextran to detect significant AD blood
biomarkers, such as amyloid-beta and phosphorylated tau. This was
accomplished by functionalizing the surface of the magnetic
nanoparticles with antibodies against amyloid-beta and phosphorylated
tau. Further studies showed that the synthesized magnetic nanoparticles
had high specificity and sensitivity when differentiating between the
healthy control group and groups with mild cognitive impairment and AD
dementia. However, the magnetic nanoparticles had moderate specificity
and sensitivity when differentiating between the mild cognitive
impairment and AD dementia groups. In the study by Chen et al., success
was found in implementing CuInS2/ZnS quantum dots
functionalized with dopamine for the detection of tau protein. Results
showed that the synthesized quantum dots had the ability to detect tau
protein concentrations as low as 9.3 pM. Another study synthesized
graphene oxide magnetic nanoparticles conjugated with tannin-capped
silver nanoparticles to detect tau tangles. These nanoparticles were
able to detect low tau concentrations of 5.74 fg/mL. Multi-walled carbon
nanotubes were also found to detect significantly low tau concentrations
of 15.0 nM in artificial cerebrospinal fluid and 7.8 nM in solution
buffer. Another study showed that surface plasmon resonance systems
synthesized with silica fibers had promising potential to detect
total-tau protein levels as low as 2.4 pg/mL and phosphorylated-tau
protein levels as low as 1.6 pg/mL. Specifically, these nanoparticulate
systems effectively differentiated between healthy controls and AD
patients and showed a 6-fold increase in total-tau levels and a 3-fold
increase in phosphorylated-tau levels between AD patients and the
healthy controls.
As shown by extensive studies, tau-targeting nanoparticles show
promising potential to function as an effective AD diagnostic tool.
However, before these nanoparticulate systems can be utilized on a
widespread clinical scale, certain limitations such as efficiency,
biosensor multiplexing, long-term biocompatibility and cost-effective
manufacturing must be overcome. Overall, coupling nanoparticle-based
diagnostics with conventional diagnostics could significantly enhance
the efficacy of AD biosensors and offer improved AD diagnostic
techniques.