In a recent study published in Science Advances, a group of researchers assessed whether dendritic spine head diameter in the temporal cortex is a better predictor of episodic memory performance in older adults than synapse quantity, accounting for β amyloid (Aβ) plaques (Clusters of protein fragments in the brain), neurofibrillary tangles (NFTs) (Twisted protein fibers inside brain cells), and sex.
Background
Episodic memory, essential for recalling personal experiences, declines with age and neurodegenerative diseases, especially due to temporal cortex injury. Dendritic spines, key postsynaptic compartments in the brain, influence synapse strength and are crucial for memory. Spine loss naturally occurs with aging, particularly in regions vital for memory, and is more strongly associated with memory impairment in Alzheimer’s disease (AD) (A progressive brain disorder causing memory loss) than Aβ plaques or NFTs.
Further research is needed to clarify how specific features of dendritic spines contribute to memory function in aging beyond the effects of natural spine loss and common neurodegenerative pathologies.
About the study
Postmortem samples of brain areas Brodmann area (BA) 6 and BA37 were obtained from participants in the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), which includes individuals who enroll without known dementia and agree to annual clinical evaluations and brain donation upon death.
The study was approved by an institutional review board at Rush University Medical Center. All participants provided informed consent, including consent for brain donation and sharing of their resources. The samples analyzed in this study covered a range of brain pathologies and cognitive scores, with appropriately sized frozen tissue samples available for experiments.
Cognitive testing of ROSMAP participants included assessments of episodic memory, perceptual speed, visuospatial ability, semantic memory, and working memory, with composite scores calculated for each domain. Additionally, the Mini-Mental State Examination (MMSE) was administered, and clinical diagnoses of major depressive disorder were made based on established criteria.
Dendritic spines and synaptic markers were visualized using Golgi-Cox staining of brain samples from BA6 and BA37. Imaging of dendrites was performed by a blinded experimenter using bright-field microscopy at high magnification. Dendritic segments meeting specific criteria were selected for analysis, and 3D digital reconstructions of dendrites and spines were conducted using specialized software. Spine morphology was classified into various categories, and quantitative measurements were collected for analysis. In total, 45,763 μm of dendrite length from 2,157 neurons were analyzed, yielding data on 55,521 individual spines.
Statistical analyses involved a multistage approach to validate the generalizability of results. Dendritic spine traits were analyzed using LASSO (Least Absolute Shrinkage and Selection Operator) regression to identify which features most significantly contributed to episodic memory performance in older adults. Cross-validation techniques ensured model accuracy, and the results were replicated in an independent sample. Spearman correlations were used to explore relationships between dendritic spine features, pathology, and memory scores, with multiple comparisons controlled for using an appropriate false discovery rate.
Study results
Dendritic spines were sampled and analyzed from the frontal and temporal cortices of 128 individuals from the ROSMAP. These postmortem samples were taken from BA6 within the premotor cortex and BA37 within the temporal cortex. The participants, who had a mean age of 90.53 ± 6.06 years, displayed varying cognitive performance scores and levels of AD-related neuropathology. Using bright-field microscopy, dendritic spine density and morphology in BA37 and BA6 tissue slices were imaged at 60X magnification and reconstructed in three dimensions. The data were then analyzed to determine the relationship between dendritic spine features and episodic memory performance.
The datasets from BA37 and BA6 were subjected to a supervised learning algorithm to identify specific dendritic spine features that might predict episodic memory performance beyond the effects of other variables, such as AD-related neuropathology. The samples were divided into a discovery set (n = 63) and a validation set (n = 62), with three cases excluded due to missing data. LASSO regression was performed on the discovery set to identify the dendritic spine features most strongly associated with episodic memory function. The analysis revealed that spine head diameter in BA37 was the most significant predictor of episodic memory performance.
The results were validated using nested model cross-validation in the replication set, confirming that models including spine head diameter, along with NFTs, neuritic Aβ plaques, and sex, provided the best prediction of episodic memory. Removing spine length, density, and volume from the model further improved its accuracy, highlighting the importance of spine head diameter in the temporal cortex for memory function.
Conversely, LASSO regression on the BA6 dataset identified spine length as the strongest predictor of episodic memory performance, although its association was weaker compared to BA37 spine head diameter. Models incorporating BA6 spine features did not perform as well, indicating that the contribution of spine head diameter to memory performance is specific to the BA37 temporal cortex.
Further analysis showed a significant positive correlation between BA37 spine head diameter and episodic memory score, even after controlling for multiple comparisons. In contrast, BA37 spine density did not significantly correlate with cognitive scores or AD-related pathology, and no significant correlations were found between BA6 spine features and cognition or pathology measures.
Conclusions
To summarize, using tissue samples from 128 ROSMAP participants, the analysis revealed that larger dendritic spine head diameters in the temporal cortex were associated with better episodic memory performance, while spine density showed no significant effect. These findings suggest that synaptic strength, rather than the number of synapses, is crucial for maintaining memory in older adults, with implications for targeted therapeutic strategies in preclinical AD.
- Courtney K. Walker et al. Dendritic spine head diameter predicts episodic memory performance in older adults.Sci. Adv.(2024).
DOI:10.1126/sciadv.adn5181 https://www.science.org/doi/10.1126/sciadv.adn5181

News
Natural Plant Extract Removes up to 90% of Microplastics From Water
Researchers found that natural polymers derived from okra and fenugreek are highly effective at removing microplastics from water. The same sticky substances that make okra slimy and give fenugreek its gel-like texture could help [...]
Instant coffee may damage your eyes, genetic study finds
A new genetic study shows that just one extra cup of instant coffee a day could significantly increase your risk of developing dry AMD, shedding fresh light on how our daily beverage choices may [...]
Nanoneedle patch offers painless alternative to traditional cancer biopsies
A patch containing tens of millions of microscopic nanoneedles could soon replace traditional biopsies, scientists have found. The patch offers a painless and less invasive alternative for millions of patients worldwide who undergo biopsies [...]
Small antibodies provide broad protection against SARS coronaviruses
Scientists have discovered a unique class of small antibodies that are strongly protective against a wide range of SARS coronaviruses, including SARS-CoV-1 and numerous early and recent SARS-CoV-2 variants. The unique antibodies target an [...]
Controlling This One Molecule Could Halt Alzheimer’s in Its Tracks
New research identifies the immune molecule STING as a driver of brain damage in Alzheimer’s. A new approach to Alzheimer’s disease has led to an exciting discovery that could help stop the devastating cognitive decline [...]
Cyborg tadpoles are helping us learn how brain development starts
How does our brain, which is capable of generating complex thoughts, actions and even self-reflection, grow out of essentially nothing? An experiment in tadpoles, in which an electronic implant was incorporated into a precursor [...]
Prime Editing: The Next Frontier in Genetic Medicine
By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc. Discover how prime editing is redefining the future of medicine by offering highly precise, safe, and versatile DNA corrections, bringing hope for more effective treatments for genetic diseases [...]
Can scientists predict life longevity from a drop of blood?
Discover how a new epigenetic clock measures how fast you are really aging from just a drop of blood or saliva. A recent study published in the journal Nature Aging constructed an intrinsic capacity (IC) clock [...]
What is different about the NB.1.8.1 Covid variant?
For many of us, Covid-19 feels like a chapter we’ve closed – along with the days of PCR tests, mask mandates and daily case updates. But while life may feel back to normal, the [...]
Scientists discover single cell creatures can learn new behaviours
It was previously thought that learning behaviours only applied to animals with complex brain and nervous systems, but a new study has proven that this may also occur in individual cells. As a result, this new evidence may change how [...]
Virus which ’causes multiple organ failure’ found at popular Spanish holiday destination
British tourists planning trips to Spain have been warned after a deadly virus that can cause multiple organ failure has been detected in the country. The Foreign Office issued the alert on its dedicated website Travel [...]
Urgent health warning as dangerous new Covid virus from China triggers US outbreak
A dangerous new Covid variant from China is surging in California, health officials warn. The California Department of Public Health warned this week the highly contagious NB.1.8.1 strain has been detected in the state, making it the [...]
How the evolution of a single gene allowed the plague to adapt, prolonging the pandemics
Scientists have documented the way a single gene in the bacterium that causes bubonic plague, Yersinia pestis, allowed it to survive hundreds of years by adjusting its virulence and the length of time it [...]
Inhalable Nanovaccines: The Future of Needle-Free Immunization
The COVID-19 pandemic highlighted the need for adaptable and scalable vaccine technologies. While mRNA vaccines have improved disease prevention, most are delivered by intramuscular injection, which may not effectively prevent infections that begin at [...]
‘Stealthy’ lipid nanoparticles give mRNA vaccines a makeover
A new material developed at Cornell University could significantly improve the delivery and effectiveness of mRNA vaccines by replacing a commonly used ingredient that may trigger unwanted immune responses in some people. Thanks to [...]
You could be inhaling nearly 70,000 plastic particles annually, what it means for your health
Invisible plastics in the air are infiltrating our bodies and cities. Scientists reveal the urgent health dangers and outline bold solutions for a cleaner, safer future. In a recent review article published in the [...]