Differences in Tau Seeding in Newborn and Adult Wild-Type Mice

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Alzheimer's disease (AD) and tauopathies are prevalent neurodegenerative conditions in older adults.
• Abnormal tau deposition is rare in children, indicating age-dependent susceptibility.
• Understanding tau seeding mechanisms is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the impact of age on tau seeding in the brain.
• To compare tau deposition in newborn versus young adult mice after inoculation with Alzheimer's disease (AD) pathology.
• To explore potential age-related factors influencing tau propagation.

Main Methods:

• Sarkosyl-insoluble fractions containing paired helical filaments (PHFs) from sporadic AD (sAD) were inoculated into the thalamus of newborn and three-month-old mice.
• Mice were analyzed at various time points (24 h to six months) post-inoculation.
• Tau-positive cells were quantified and characterized in different age groups.

Main Results:

• Tau-positive cells were scarce and diminished over time in mice inoculated as newborns.
• Significant tau-positive cell accumulation, including neurons and oligodendrocytes, occurred in mice inoculated at three months of age.
• Newborn mice re-inoculated at three months showed similar tau seeding to those inoculated only at three months.

Conclusions:

• Age significantly influences the susceptibility to tau seeding, with young adults being more vulnerable than newborns.
• Differences in tau seeding may be linked to age-related shifts in tau protein isoforms (3Rtau/4Rtau) and brain maturity.
• Early-life inoculation with AD PHFs does not confer protection against subsequent tau seeding in young adult mice.